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International audience; Congenital anomalies of the kidney and urinary tract (CAKUT) constitute one of the most frequent birth defects and represent the most common cause of chronic kidney disease in the first three decades of life. Despite the discovery of dozens of monogenic causes of CA-KUT, most pathogenic pathways remain elusive. We performed whole-exome sequencing (WES) in 551 individuals with CAKUT and identified a heterozygous de novo stop-gain variant in ZMYM2 in two different families with CAKUT. Through collaboration, we identified in total 14 different heterozygous loss-of-function mutations in ZMYM2 in 15 unrelated families. Most mutations occurred de novo, indicating possible interference with reproductive function. Human disease features are replicated in X. tropicalis larvae with morpho-lino knockdowns, in which expression of truncated ZMYM2 proteins, based on individual mutations, failed to rescue renal and cranio-facial defects. Moreover, heterozygous Zmym2-deficient mice recapitulated features of CAKUT with high penetrance. The ZMYM2 protein is a component of a transcriptional corepressor complex recently linked to the silencing of developmentally regulated endoge-nous retrovirus elements. Using protein-protein interaction assays, we show that ZMYM2 interacts with additional epigenetic silencing complexes, as well as confirming that it binds to FOXP1, a transcription factor that has also been linked to CAKUT. In summary, our findings establish that loss-of-function mutations of ZMYM2, and potentially that of other proteins in its interactome, as causes of human CAKUT, offering new routes for studying the pathogenesis of the disorder.

Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease in the first three decades of life, and in utero obstruction to urine flow is a frequent cause of secondary upper urinary tract malformations. Here, using whole-exome sequencing, we identified three different biallelic mutations in CHRNA3, which encodes the α3 subunit of the nicotinic acetylcholine receptor, in five affected individuals from three unrelated families with functional lower urinary tract obstruction and secondary CAKUT. Four individuals from two families have additional dysautonomic features, including impaired pupillary light reflexes. Functional studies in vitro demonstrated that the mutant nicotinic acetylcholine receptors were unable to generate current following stimulation with acetylcholine. Moreover, the truncating mutations p.Thr337Asnfs(∗)81 and p.Ser340(∗) led to impaired plasma membrane localization of CHRNA3. Although the importance of acetylcholine signaling in normal bladder function has been recognized, we demonstrate for the first time that mutations in CHRNA3 can cause bladder dysfunction, urinary tract malformations, and dysautonomia. These data point to a pathophysiologic sequence by which monogenic mutations in genes that regulate bladder innervation may secondarily cause CAKUT.

Summary Introduction Relative Energy Deficiency in Sport (RED-S) is a clinical syndrome that includes the many complex health and performance consequences of low energy availability (EA) in athletes, when there is insufficient caloric intake to meet exercise-related energy expenditure and to support basic physiologic functions. There is a high prevalence of urinary incontinence (UI) in female athletes and it is more common in female athletes than non-athletes. The objective of this study was to determine if low EA is associated with UI in a population of adolescent and young adult female athletes and to evaluate for an association between sport categories and UI. Material and methods 1000 nulliparous female patients, ages 15–30 years, presenting to a sports medicine subspecialty clinic, provided informed consent/assent to participate in a cross-sectional study involving a comprehensive survey, anthropomorphic measurements, and medical record review. Low EA was defined as meeting ≥1 criterion: self-reported history of eating disorder/disordered eating (ED/DE), and/or a high score on the Brief Eating Disorder in Athletes Questionnaire (BEDA-Q), and/or a high score on the Eating Disorder Screen for Primary Care (ESP). UI was assessed using questions adapted from the International Consultation on Incontinence-Urinary Incontinence Short Form (ICIQ-UI-SF), questions regarding timing of UI onset/duration, and a binary question regarding UI during sport activities. A total of 36 sport types were included in the survey and sub-divided into categories. Results and discussion Of the 1000 female athletes surveyed, 165 (16.5%) reported a history of experiencing UI during athletic activities. ICIQ- UI-SF responses indicated that 14% (137/1000) of the cohort experienced slight incontinence, 4% (35/1000) moderate incontinence, and 2 athletes experienced severe incontinence. There was a significant difference between UI categories in age (p = 0.01), low EA (p Conclusions UI during athletic activities is a common problem among nulliparous adolescent and young adult female athletes, occurring in 16.5% of female athletes surveyed. UI was significantly associated with low EA across all sport categories. Sport type was significantly associated with UI, with the highest impact sport group demonstrating a higher prevalence and symptom severity compared to other sport categories. Summary Table . Characteristics of Female Athletes with Urinary Incontinence Entire cohort N = 1000 Athletes with Urinary incontinence n = 165 (16.5%) P-value Freq. (%) Freq. (%) Low energy availability 473 (47%) 99 (20.9%) Menstrual dysfunction 449 (45%) 80 (17.8%) 0.31 Sport category: High impact 49 (5%) 18 (36.7%) Ball/field 356 (36%) 46 (12.9%) Non-weightbearing endurance 60 (6%) 6 (10.0%) Aesthetic 173 (17%) 25 (14.5%) Resistance/power 106 (11%) 23 (21.7%) Running 222 (22%) 44 (19.8%) Technical 34 (3%) 3 (8.8%)

Human studies have shown loss of diversity of the gut microbiome following hematopoietic stem cell transplantation (HSCT) in association with significant gut injury caused by the preparative regimen. Prolonged antibiotic use worsens loss of microbiome diversity and increases risk of complications such as graft-versus-host disease (GVHD). Our data support the hypothesis that loss of intestinal commensals that produce short-chain fatty acids (SCFAs) may increase dysbiosis. Here, we report an extensive longitudinal examination of changes in the luminal SCFAs in children undergoing allogeneic HSCT, and the relationship of those changes to the microbiota and antibiotic exposure. We found significant and progressive alterations in butyrate, and in additional SCFAs in stool in the first 14 days after transplant, a finding not observed in published mouse studies. SCFA levels were lower in children receiving antibiotics with activity against anaerobic organisms. Moreover, day 14 post-HSCT butyrate and propionate levels are lower in children who went on to develop GVHD, although our disease population was small. These data provide insight into the mechanism of prior observations that loss of diversity and increased antibiotic use are associated with GVHD following HSCT. Our findings offer potential modifiable targets to reduce risk of GVHD and improve survival after HSCT.

Aims: To introduce the standard procedure of cystometry and interpretation of the results in children. Methods: The literature on cystometry in children in PubMed for the last 20 years was reviewed. The updated knowledge regarding indication, preparation, technique, and interpretation of cystometry in children were summarized. Results: Filling cystometry is the core content of a paediatric urodynamic study. In this section, the technique for performing cystometry is introduced in details. Emphasis is placed on correctly setting up the equipment according to ICS and ICCS guidelines, using appropriate terminology, providing indications for its performance with specific considerations for children, and proper interpretation of results. Conclusions: Cystometry can be used in children including newborn to evaluate lower urinary tract dysfunction.

To investigate the correlation between urethral instability (URI) and overactive bladder (OAB) in children. We retrospectively investigated 126 children with OAB and 36 children without OAB using synchro-cystourethrometry. The prevalence of detrusor overactivity (DO) and URI, and the diagnostic sensitivity of DO alone and DO combined with URI, was compared. The OAB children with URI voluntarily received transcutaneous electrical pudendal nerve stimulation with anisodamine (stimulation group, SG) or anisodamine alone (non-stimulation group, NSG). The effectiveness of treatment was evaluated. Average voided volume (AVV), maximum voided volume (MVV), and number of voids per day (NV) were collected and analyzed. In OAB children, the prevalence of DO and URI was 51.6 and 32.5%, respectively. The prevalence of URI was 5.6% in controls. The prevalence of URI was significantly higher in OAB children. The diagnostic sensitivity and Youden index of DO combined with URI were higher than DO alone. In SG, 45.7% of children were cured, with a ≥ 50% improvement rate of 82.9%, while no child was cured, with a ≥ 50% improvement rate of 36.8% in NSG. A significant increase in AVV and MVV together, with a decrease in NV, was seen in SG. There was a significant difference in visual analogue scale values between SG and NSG (P

Patients with a history of intravenous drug abuse included in an official opioid substitution program represent an important subgroup of patients with chronic hepatitis C. The objective of this study was to assess the efficacy of and adherence to treatment with peginterferon and ribavirin in Austrian patients on stable opioid substitution therapy (OST). This prospective, multicenter, observational, non-interventional trial (clinicaltrials.gov identifier, NCT01416610) included treatment-naive patients with chronic hepatitis C on OST. Treatment consisted of peginterferon alpha-2a (PEGASYS®, 180 µg/week) plus ribavirin (COPEGUS®, 1000/1200 mg/day in genotypes (GT) 1/4 and 800 mg/day in GT 2/3) for 24–72 weeks, according to GT and viral response. The intention-to-treat (ITT) population comprised 88 patients. Mean duration of therapy was 6.0 ± 2.8 months. Treatment was discontinued earlier than planned in 34 out of 88 patients (39%), mainly because of poor adherence or side effects of treatment. At the end of treatment 65/88 patients (74%) were PCR negative. During follow-up, 5 patients relapsed. Only 44/88 patients (50%) could be evaluated 24 weeks after the end of treatment. Sustained virologic response 24 weeks after end of therapy (SVR24) was documented in 39/88 patients (44%). If only patients were considered who finished treatment as planned and for whom results at follow-up week 24 were available, the SVR24 rate was 89% (32/36). Despite favorable prognostic factors, such as young age and a high proportion of GT3, SVR rates were low in this cohort of patients receiving OST, the main reason being poor adherence; however, in those patients completing treatment, the SVR rate was high.

BACKGROUND: Independent associations between chronic liver disease, MELD, and postoperative outcomes among patients selected for liver resection have not been completely established. We hypothesized independent associations between MELD, cirrhosis, and postoperative mortality. METHODS: Patient-level data from the targeted hepatectomy module and ACS NSQIP PUF during 2014–2015 were merged. Multivariable regression models with interaction effect between MELD and liver texture (normal vs congested/fatty vs cirrhotic) tested the independent effects of covariates on mortality and morbidity. RESULTS: 3,530 patients were included, of whom 668 patients (19%) had cirrhosis. ACS NSQIP defined mortality (3.9%vs1.1%) and morbidity (23.5%vs15.8%) were higher in patients with cirrhosis (both p

Pictures are often used in cognitive research to represent objects and many species have demonstrated the ability to recognize two-dimensional pictures as representations of their three-dimensional counterparts. However, for ursids picture recognition has been reported in only one study of a single 11-year-old female American black bear (Johnson-Ulrich et al. 2016). We tested the picture recognition abilities of an additional species, the sloth bear. After a food preference test by which the bears' food options were ranked and categorized as high-, mid-, and low-preference items, we tested a sub-adult male and an adult female sloth bear by presenting two pictures of food in each testing trial-a high-preference food and a low-preference food. Both bears met the criterion by choosing the pictures of their preferred foods in at least 80% of the trials in three consecutive testing sessions. We then presented never-before-used pictures of high-preference versus low-preference food items and they again met our criterion.

Aims: A pilot survey shows that primary nocturnal enuresis (PNE) prevalence has increased significantly during the past decade in Mainland China. Whether it is related to the delay of elimination communication (EC) is unclear. This study retrospectively investigated the influence of delayed EC on the PNE prevalence in children and adolescents in mainland China. Methods: A cross-sectional study of PNE prevalence was performed by distributing 19 500 anonymous self-administered questionnaires to parents in five provinces of mainland China from July 2017 to October 2017. The questionnaires included sociodemographic data, family caregivers’ information, and details about the disposable diapers (DD) usage, EC commencement date, psychological disorders, lower urinary tract symptoms, and family history of PNE in children and adolescents. The 2017 PNE prevalence was compared with that of 2006 in Mainland China. Results: The total response rate was 97.04% (18 631 of 19 500) and 92.39% (18 016 of 19 500) qualified for statistical analysis. The PNE prevalence in 2017 has increased significantly compared to that of 2006 (7.30% vs 4.07%, P < 0.001). The PNE prevalence in children with EC starting before 6 months of age was significantly lower than those who start after 12 months of age. The longer DD were used and the later the beginning of EC, the higher the PNE prevalence was found. Conclusions: The PNE prevalence in Mainland China has increased significantly during the past 10 years. A longer use of DD and later onset of EC may be risk factors for PNE.

To examine whether the daily consumption of normal-protein (NP) vs higher-protein (HP) breakfasts improve free-living glycemic control in overweight/obese, 'breakfast skipping' adolescents. Twenty-eight healthy, but overweight, teens (age: 19±1 year; BMI: 29.9±0.8 kg m(-2)) completed a 12-week randomized parallel-arm study in which the adolescents consumed either a 350 kcal NP breakfast (13 g protein) or HP breakfast (35 g protein). Pre- and post-study 24-h blood glucose measures were assessed using continuous glucose monitoring. Although no main effects of time or group were detected, time by group interactions were observed. Post hoc pairwise comparisons assessing the post-pre changes revealed that the daily consumption of the HP breakfasts tended to reduce the 24-h glucose variability (s.d.) vs NP (-0.17±0.09 vs +0.09±0.10 s.d.; P=0.06) and tended to reduce the time spent above the high glucose limit (-292±118 vs -24±80 min; P=0.09). The consumption of the HP breakfasts also reduced the 24-h maximal (peak) glucose response (-0.94±0.36 vs +0.30±0.18 mmol l(-1); P0.01) and reduced postprandial glucose fluctuations (-0.88±0.44 vs +0.49±0.34 mmol l(-1); P0.03) vs NP. These data suggest that the daily addition of a HP breakfast, containing 35 g of high-quality protein, has better efficacy at improving free-living glycemic control compared with a NP breakfast in overweight/obese, but otherwise healthy, 'breakfast skipping' adolescents.

Summary Introduction Stress urinary incontinence (SUI) is common among older multiparous females but rarely reported in active, young girls. Objectives Our hypothesis is: physically active adolescent females develop pelvic floor laxity demonstrable on upright VCUG. Our objectives are to (1) increase awareness of SUI in young females, (2) test our hypothesis with an upright VCUG, and (3) report effectiveness of step-wise management. Study design A retrospective review was performed of nulliparous girls with only SUI seen from 2000 to 2015, who were evaluated with upright voiding cystourethrography (VCUG) (bladder descent defined as ≥2 cm drop of bladder neck below pubic ramus at capacity). Data collection included level of physical activity, physical examination, BMI and Z-scores, urodynamics, management, and treatment response. Standard urotherapy (SUT) (timed voiding, proper diet, adequate fluids, bowel management) and biofeedback therapy (BFT) was initiated. Fisher exact test was used to calculate ‘p’ values. Results Thirty-three females (median age 15.1 years, range 5.5–20.3) were identified who underwent an upright VCUG; 20 had bladder neck descent (Fig.). Of these 20, 15 (75%) were involved in strenuous activity, whereas only three of 13 (23%) without descent engaged in intense athletics. No differences were noted in median BMI and Z-score with strenuous activity (21.1 (15.2–26.7) and 0.31 (−0.9–1.94)), respectively, versus patients without (21.3 (15.8–33.5) and 0.62 (−0.0–2.38)). Average follow-up for all was 16.6 months (range 0.4–102.2). Of 20 demonstrating bladder neck descent, three did not complete therapy and were lost to follow-up. Only six of these 17 became dry. Of the remaining 11, eight underwent surgery: Burch colposuspension (5), fascial sling (2), Coaptite to the bladder neck (1), and an artificial urinary sphincter (1). This latter girl had a failed Burch colposuspension 1 year previously. All surgical patients are dry. Of 13 without bladder descent on VCUG, five did not complete therapy and were lost to follow-up. The remaining eight were managed non-surgically; seven were fully dry at last follow-up. Overall, 13 of 25 (52%) achieved dryness. SUT and BFT were more effective in those without, than in those with bladder descent (87.5% vs. 35.3%, p = 0.0302, Fisher exact test). Discussion and conclusions Physically active, nulligravid girls with SUI can be efficaciously diagnosed on upright VCUG. They should be considered for non-surgical therapy but will likely require bladder neck elevating surgery. Non-surgical therapy works for those with minimal bladder descent on cystography. Download : Download high-res image (325KB) Download : Download full-size image Figure Results of various treatments in 33 females with (SUI), in relation to their VCUG findings. Note *=1 girl who failed a Burch procedure then had placement of an artificial urinary sphincter. Also note the success rate, or lack thereof, for biofeedback training to strengthen the pelvic floor musculature in those girls with and without pelvic floor descent.

Aims As awareness and frequency of tethered spinal cord (TSC) related to occult spinal dysraphism (OSD) has increased with magnetic resonance imaging (MRI), variability exists in its evaluation and management. Due to no published level I data, we summarize the current International Children's Continence Society (ICCS) recommendations for diagnosis and treatment of OSD. Methods Guidelines were formulated based on analysis of pertinent literature and consensus among authors. This document was vetted by the multidisciplinary members of the ICCS via its website before submission for peer review publication. Results The more frequent diagnosis of OSD is associated with increased operative intervention. Spinal cord untethering (SCU) has a highly variable risk profile, largely dependent on the specific form of OSD. Progressive neurological deterioration attributed to “tethered cord” may occur, with or without surgery, in selected forms of OSD whereas other cohorts do well. Conclusion Infants with classic cutaneous markers of OSD, with progressive neurologic, skeletal, and/or urologic findings, present no diagnostic or therapeutic dilemma: they routinely undergo MRI and SCU. Conversely, in asymptomatic patients or those with fixed, minor abnormalities, the risk profile of these OSD cohorts should be carefully considered before SCU is performed. Irrespective of whether or not SCU is performed, patients at risk for progression should be followed carefully throughout childhood and adolescence by a multidisciplinary team.

Concern in patients with bladder exstrophy after reconstruction regarding potential injury to pelvic neurourological anatomy and a resultant functional deficit prompted combined (simultaneous) cystometrography and electromyography after complete primary repair of bladder exstrophy. We determined whether complete primary repair of bladder exstrophy would adversely affect the innervation controlling bladder and external urethral sphincter function.Complete primary repair of bladder exstrophy was performed via a modified Mitchell technique in newborns without osteotomy. Postoperative evaluation included combined cystometrography and needle electrode electromyography via the perineum, approximating the external urethral sphincter muscle complex. Electromyography was done to evaluate the external urethral sphincter response to sacral reflex stimulation and during voiding.Nine boys and 4 girls underwent combined cystometrography/electromyography after complete primary repair of bladder exstrophy. Age at study and time after complete primary repair of bladder exstrophy was 3 months to 10 years (median 11.5 months). Cystometrography revealed absent detrusor overactivity and the presence of a sustained detrusor voiding contraction in all cases. Electromyography showed universally normal individual motor unit action potentials of biphasic pattern, amplitude and duration. The external urethral sphincter sacral reflex response was intact with a normal caliber with respect to Valsalva, Credé, bulbocavernosus and anocutaneous (bilateral) stimulation. Synergy was documented by abrupt silencing of external urethral sphincter electromyography activity during voiding.After complete primary repair of bladder exstrophy combined cystometrography/electromyography in patients with bladder exstrophy showed normal neurourological findings, including sacral reflex responses, sustained detrusor voiding contraction and synergic voiding, in all patients postoperatively. These findings confirm the safety of complete primary repair of bladder exstrophy. Based on our results we have discontinued routine electromyography in these patients.

PURPOSE: We present a consensus view of members of the International Children's Continence Society (ICCS) together with pediatric gastroenterologists, experts in the field of functional gastrointestinal disorders, on the management of functional constipation in children with lower urinary tract symptoms.MATERIALS AND METHODS: Discussions were held by the board of the ICCS and a multidisciplinary core group of authors was appointed. The draft document review process was open to all ICCS members via the website. Feedback was considered by the core authors and, by agreement, amendments were made as necessary.RESULTS: Guidelines on the assessment, and pharmacological and nonpharmacological management of functional constipation in children with lower urinary tract symptoms are outlined.CONCLUSIONS: The final document is not a systematic literature review. It includes relevant research when available, as well as expert opinion on the current understanding of functional constipation in children with lower urinary tract symptoms. The document is intended to be clinically useful in primary, secondary and tertiary care settings.

Background Children with urinary incontinence (UI) have associated functional constipation (FC) and fecal incontinence (FI). The physiology between lower urinary tract (LUT) and anorectum in children has not been elucidated. Aims: Observe the effect of rectal distention (RD) on LUT function, and bladder filling and voiding on anorectal function. Methods Children with voiding dysfunction referred to Boston Children's Hospital were prospectively enrolled in combined urodynamic (UDS) and anorectal manometry (ARM). Anorectal and urodynamic parameters were simultaneously measured. Patients underwent two micturition cycles, first with rectal balloon deflated and second with it inflated (RD). Lower urinary tract and anorectal parameters were compared between cycles. Key Results Ten children (seven UI, four recurrent UTIs, nine FC ± FI) were enrolled. Postvoid residual (PVR) increased (p = 0.02) with RD. No differences were observed in percent of bladder filling to expected bladder capacity, sensation, and bladder compliance with and without RD. Bladder and abdominal pressures increased at voiding with RD (p < 0.05). Intra-anal pressures decreased at voiding (p < 0.05), at 25% (p = 0.03) and 50% (p = 0.06) of total volume of bladder filling. Conclusions & Inferences The PVR volume increased with RD. Stool in the rectum does not alter filling cystometric capacity but decreases the bladder's ability to empty predisposing patients with fecal retention to UI and UTIs. Bladder and abdominal pressures increased during voiding, demonstrating a physiological correlate of voiding dysfunction. Intra-anal pressures decreased during bladder filling and voiding. This is the first time intra-anal relaxation during bladder filling and voiding has been described.

Recent data comparing prenatal to postnatal closure of myelomeningocele showed a decreased need for ventriculoperitoneal shunting and improved lower extremity motor outcomes in patients who underwent closure prenatally. A total of 11 children whose spinal defect was closed in utero were followed at our spina bifida center. We hypothesized that in utero repair of myelomeningocele improves lower urinary tract function compared to postnatal repair.Eleven patients who underwent in utero repair were matched to 22 control patients who underwent postnatal repair according to age, gender and level of spinal defect. Urological outcomes were retrospectively reviewed including urodynamic study data, need for clean intermittent catheterization, use of anticholinergic agents and prophylactic antibiotics, and surgical history. The need for ventriculoperitoneal shunting or spinal cord untethering surgery was also reviewed.Mean followup was 7.2 years for patients who underwent in utero repair and 7.3 years for those who underwent postnatal repair. Mean patient age at compared urodynamic studies was 5.9 years for in utero repair and 6.0 years for postnatal repair. The in utero repair group was comprised of 5 lumbar and 6 sacral level defects with equal matching (1:2) in the postnatal repair cohort. There were no differences between the groups in terms of need for clean intermittent catheterization, incontinence between catheterizations or anticholinergic/antibiotic use. Urodynamic parameters including bladder capacity, detrusor pressure at capacity, detrusor overactivity and the presence of detrusor sphincter dyssynergia were not significantly different between the groups. There was no difference in the rate of ventriculoperitoneal shunting (p = 0.14) or untethering surgery (p = 0.99).While in utero closure of myelomeningocele has been shown to decrease rates of ventriculoperitoneal shunting and improve motor function, it is not associated with any significant improvement in lower urinary tract function compared to repair after birth.

We investigated associated urodynamic abnormalities in toilet trained children with vesicoureteral reflux.A total of 298 toilet trained children with primary vesicoureteral reflux underwent urodynamic evaluation. Urodynamic parameters were reviewed and correlated with age, gender, presence of lower urinary tract symptoms and reflux severity.Symptomatic lower urinary tract symptoms were present in 111 children (37.2%, group 1). Children with lower urinary tract symptoms had significantly decreased severity of vesicoureteral reflux compared to children without these symptoms (187 patients, group 2). The majority of the patients had normal early bladder compliance regardless of presence of lower urinary tract symptoms or reflux grade. On the other hand, decreased late bladder compliance was more common in group 1 vs group 2. Ratio of cystometric bladder capacity to expected bladder capacity was higher in group 2. Detrusor overactivity was observed in 28.5% of the children, and the incidence was significantly higher in group 1 vs group 2, and in mild vs moderate or severe reflux. Dysfunctional voiding from bladder sphincter dyscoordination was seen in 32% of children 2.5 to 4 years old with vesicoureteral reflux and lower urinary tract symptoms, compared to 8% in children 5 to 16 years old.The presence of lower urinary tract symptoms in children with vesicoureteral reflux correlated well with some urodynamic findings suggestive of overactive bladder and negatively correlated with reflux severity. In contrast, dysfunctional voiding was more common in younger children with reflux and lower urinary tract symptoms. These findings suggest that treatment of voiding dysfunction should be directed toward the specific type of abnormality in children with vesicoureteral reflux.

We prospectively evaluated the precision of ultrasound and computerized tomography to diagnose urinary stones in children and determined whether these differences in radiological findings have any impact on clinical management.A total of 50 consecutive patients with suspected urolithiasis underwent computerized tomography and ultrasound. Two radiologists reviewed each study independently in blinded fashion. When a difference in findings was detected, 8 pediatric urologists reviewed the case. Clinical management was based on the results of each radiological test independently. Statistical analysis was performed using Fisher's exact test.Compared to computerized tomography ultrasound had 76% sensitivity and 100% specificity. In 8 patients stone(s) seen on computerized tomography was not seen on ultrasound. The average size of missed stones was 2.3 mm. In 7 patients computerized tomography showed stones bilaterally but stone was seen on only 1 side on ultrasound. When evaluating the clinical impact, the ultrasound/computerized tomography discrepancy did not result in any significant change in clinical management except in 4 cases. In these cases ultrasound findings suggested that additional imaging was required and, thus, stone(s) in the distal ureter would have been identified on subsequent imaging.Although computerized tomography is more sensitive for detecting urolithiasis than ultrasound, the difference in usefulness between the 2 radiological tests may not be clinically significant. Given concerns for the potentially harmful cumulative long-term effect of radiation, ultrasound should be considered the first imaging test in children with suspected urolithiasis.

The natural history of caliceal diverticula in children is unknown. We review our series of children with caliceal diverticula to examine the presentation, natural history and management.We retrospectively reviewed the records of 22 children presenting with caliceal diverticula between 1983 and 2006. All pertinent clinical data were recorded, including demographics, imaging studies, treatment and clinical outcome.A total of 22 children had 23 caliceal diverticula. There were 14 girls and 8 boys who presented at a mean age of 5.4 +/- 3.1 years (range 0.2 to 12). At clinical presentation 10 patients had febrile urinary tract infection, 2 had hematuria, 2 had abdominal pain, 1 had flank pain and 8 were asymptomatic. Mean diameter of all caliceal diverticula was 2.2 +/- 1.7 cm. All patients underwent voiding cystourethrogram. Two patients (9%) had concomitant ipsilateral caliceal diverticula and vesicoureteral reflux. A total of 10 patients with caliceal diverticula (43%) were treated at a mean of 3.0 +/- 2.3 years after initial presentation due to symptomatic enlargement in 5, symptomatic calculus in 3, complicated abscess in 1 and urosepsis in 1. Treatment modalities included percutaneous ablation, open marsupialization/ablation, partial nephrectomy and laparoscopic marsupialization/ablation. There were no recurrences during a mean followup of 3.1 +/- 2.9 years (range 0.1 to 10.1) in these 10 patients. In the 13 caliceal diverticula (57%) that were observed mean followup was 6 +/- 3.7 years (range 1.2 to 10.5). These caliceal diverticula were stable in size and remained asymptomatic.Caliceal diverticula in children are rare. Most caliceal diverticula remain stable and asymptomatic but approximately 20% may have symptomatic enlargement that may warrant surgical management. Given the morbidity associated with caliceal diverticula and concomitant vesicoureteral reflux, evaluation for ipsilateral reflux is mandatory. Overall approximately 43% of children with caliceal diverticula require surgical intervention, and various treatment options are available.

The purpose of this prospective study was to assess whether outcome of speech and language in children 5-10 years after corrective surgery for tetralogy of Fallot (TOF) or ventricular septal defect (VSD) in infancy was influenced by the preoperative condition of hypoxemia or cardiac insufficiency and whether it was associated with perioperative risk factors and neurodevelopmental outcome. A total of 35 unselected children, 19 with TOF and hypoxemia and 16 with VSD and cardiac insufficiency, operated with combined deep hypothermic circulatory arrest and low-flow cardiopulmonary bypass at mean age 0.7+/-0.3 (mean+/-standard deviation) years, underwent, at mean age 7.4+/-1.6 years, standardized evaluation of speech and language functions. Results were compared between subgroups and related to perioperative factors, sociodemographic and neurodevelopmental status. Age at testing, socioeconomic status and history of speech and language development were not different between the subgroups. In contrast, total scores on oral and speech motor control functions (TFS) as well as on oral and speech apraxia (Mayo Test) were significantly reduced (p

Summary Background The pathogenesis of the chronic inflammatory skin disease hidradenitis suppurativa (HS, also known as acne inversa) involves epidermal alterations such as psoriasiform epidermal hyperplasia and keratin plugging. Keratinocytes are an important source of proinflammatory molecules in inflammatory skin diseases and can be stimulated by interleukin (IL)-17+ cells. Objectives To explore the possible role of the epithelium in the pathogenesis of HS. Methods We performed immunohistochemical stainings and Western blot experiments to investigate the localization and expression of inflammation-associated molecules, including the cytokine IL-17, components of the inflammasome including caspase-1, and the endogenous danger-associated molecular pattern molecules S100A8 and S100A9 (calprotectin). To examine a possible effect of upregulated proinflammatory cytokines on the inflammatory infiltrate, differences in the cellular composition of perifollicular and deep dermal infiltrates were analysed. Results The number of IL-17+ cells is increased in lesional and perilesional HS skin. The epidermis produces proinflammatory molecules and shows an upregulated expression of components of the NLRP3 inflammasome, activated caspase-1 and expression of S100A8/S100A9. Additionally, the course of the inflammatory process in HS involves influx of innate immune cells, particularly IL-17-expressing neutrophils. Conclusions IL-17-producing cells are present in lesional and perilesional HS skin and may contribute to the initiation of inflammatory processes. Furthermore, the epidermis is a source of proinflammatory cytokines, shows inflammasome activation and expresses S100A8/S100A9, thereby possibly contributing to the propagation of inflammation. A massive influx of IL-17-expressing neutrophils is observed in the deep infiltrate.

Summary Background Sacral agenesis (SA) is a rare congenital condition that refers to the absence of part or all of two or more lower sacral vertebral bodies. It can be associated with neurogenic bladder dysfunction that does not necessarily correlate with the level of spinal or skeletal defect. Patients with SA should undergo urodynamic studies (UDS) to guide lower urinary tract (LUT) management. Objective This review aimed to update the present institutional experience since 1981 of this rare patient population with detailed, long-term follow-up of bladder and kidney function. Study design A single institution, retrospective, IRB-approved review was performed on patients born after January 1, 1981 with an isolated diagnosis of sacral agenesis without spina bifida, and followed with urologic involvement at Boston Children's Hospital. Records were reviewed for demographics, radiologic imaging, UDS including cystometrogram (CMG) and electromyography (EMG), surgery, and blood chemistries. Comparisons were made between groups of patients based on age at diagnosis, with specific focus on renal function and stability of neurogenic bladder lesion. Results Forty-three patients were identified: 23 female and 20 male. Thirty-seven children (86%) had a known age of diagnosis. Nineteen were diagnosed before 2 months old, including five who were diagnosed prenatally, 11 were diagnosed between 2 and 18 months, and seven were diagnosed after 18 months. All 43 had UDS, with 24 (55.8%) studied at the time of diagnosis ( Summary Table ). Twenty had serial full UDS, with 30% demonstrating neurourologic instability. None developed end-stage renal disease (ESRD) or required spinal cord detethering. Discussion Many children with SA appeared to be diagnosed prenatally or early in life; SA was mostly identified during evaluation of associated anomalies. Though UDS aid in urologic management, testing was not routinely utilized at the time of diagnosis. Conclusions This review of long-term follow-up in SA patients showed stable LUT and renal function, with minimal risk of progression to ESRD. Summary Table . Group 1 Group 2 Group 3 Group 4 Adjusted P-value Age at diagnosis 2–18 months >18 months unknown n 19 11 7 6 Most recent method of bladder emptying Voiding 7 (36.8%) 3 (27.3%) 2 (28.6%) 1.00 CIC 13 (68.4%)* 8 (72.7%) 5 (71.4%) 1.00 No hydronephrosis on recent ultrasound 13 (68.4%) 5 (45.5%) 3 (42.8%) 0.90 Recent serum creatinine (ng/dl) Median 0.4 0.4 0.55 0.91 IQR 0.3–0.5 0.4–0.7 0.4–0.8 0.91 *One patient utilized both CIC and voiding to empty.

Introduction Existing survey instruments for bowel dysfunction in the pediatric population are either parent-reported or focus on non-neurogenic bowel dysfunction. Objective The purpose of this study was to develop and validate an adolescent-reported survey to assess the severity of bowel dysfunction in spina bifida patients and examine its impact on quality of life (QOL). Study design We performed a cross-sectional study of patients in our Myelodysplasia Program, aged 11–17 years, with a history of constipation and/or fecal incontinence (FI) from November 2010 to June 2013. Control patients, aged 11–17 years, were recruited from the stone clinic. Exclusion criteria were lack of English fluency, insufficient reading skills, or an incontinent fecal diversion. A 29-item version of the Adolescent Fecal Incontinence and Constipation Symptom Index (A-FICSI) was developed with five domains (Figure). Test re-test reliability and correlation with the total global health-related QOL score from the Parkin survey were measured using the Pearson correlation coefficient. A factor analysis model with four-fold correlations was tested. Results Of the 65 study-eligible individuals approached, 25 (11 boys) completed the A-FICSI (median age 12.6 years, IQR 11.8–14.7 years) and 17 completed another survey on urinary incontinence (64.6% response rate). Twenty-one control patients with nephrolithiasis completed the A-FICSI. Nine of the 25 completed a second administration of the survey. The mean correlation between repeated administrations of the survey was r = 0.43. There was a significant negative correlation between severity of constipation (r = −0.299, p 0.30) in the predicted direction. Unstandardized residuals were 8.7% (95% CI 6.4–10.9%). Item reduction was performed on the 29-item instrument based on results of the factor analysis. The finalized instrument contained 21 items. Discussion This is the first adolescent-reported bowel dysfunction instrument to undergo formal psychometric assessment in the spina bifida population. The instrument demonstrated adequate reliability and the five-factor structure fit the data well. This study highlights the negative impact of bowel dysfunction on the QOL of spina bifida patients. It is limited by the moderate sample size that is a common issue in relatively rare diseases. Conclusion The A-FICSI possesses desirable psychometric properties for the measurement of bowel dysfunction in the spina bifida population. Figure. Conceptual model of the Adolescent Fecal Incontinence and Constipation Symptom Index. Figure options Download full-size image Download high-quality image (276 K) Download as PowerPoint slide

We compared urodynamic findings in patients who underwent prenatal closure of myelomeningocele with those of patients who underwent postnatal closure, and equivalent lower urinary tract evaluations.Urodynamic studies of 5 patients (2 boys, 3 girls) who underwent prenatal closure of myelomeningocele were compared to those of 88 patients with similar level lesions who underwent repair postnatally between 1979 and 2002.All 5 patients in the prenatally treated cohort had lower lumbosacral lesions on neurological examination. These patients displayed no evidence of electromyographic activity, indicating complete denervation of the external sphincter. In comparison 34 of the 88 patients in the postnatal cohort (39%) lacked sphincter activity at newborn examination, with similar findings noted at 1-year evaluation. In terms of bladder function all 5 patients in the prenatal cohort exhibited detrusor overactivity, compared to 33 of the 88 patients (38%) in the postnatal cohort at the newborn examination, with similar findings at 1-year evaluation.Fetal closure of myelomeningocele is associated with a higher incidence of complete denervation of the external urethral sphincter and detrusor overactivity compared to postnatal closure. Patients who undergo this novel procedure should undergo urodynamic studies in the immediate newborn period and should be under close postnatal surveillance to document possible tethering of the spinal cord, urinary incontinence and increased detrusor pressures.

Summary Background Patients with end-stage bladder disease can be treated with cystoplasty using gastrointestinal segments. The presence of such segments in the urinary tract has been associated with many complications. We explored an alternative approach using autologous engineered bladder tissues for reconstruction. Methods Seven patients with myelomeningocele, aged 4–19 years, with high-pressure or poorly compliant bladders, were identified as candidates for cystoplasty. A bladder biopsy was obtained from each patient. Urothelial and muscle cells were grown in culture, and seeded on a biodegradable bladder-shaped scaffold made of collagen, or a composite of collagen and polyglycolic acid. About 7 weeks after the biopsy, the autologous engineered bladder constructs were used for reconstruction and implanted either with or without an omental wrap. Serial urodynamics, cystograms, ultrasounds, bladder biopsies, and serum analyses were done. Results Follow-up range was 22–61 months (mean 46 months). Post-operatively, the mean bladder leak point pressure decrease at capacity, and the volume and compliance increase was greatest in the composite engineered bladders with an omental wrap (56%, 1·58-fold, and 2·79-fold, respectively). Bowel function returned promptly after surgery. No metabolic consequences were noted, urinary calculi did not form, mucus production was normal, and renal function was preserved. The engineered bladder biopsies showed an adequate structural architecture and phenotype. Conclusions Engineered bladder tissues, created with autologous cells seeded on collagen-polyglycolic acid scaffolds, and wrapped in omentum after implantation, can be used in patients who need cystoplasty.

The renal histologic changes associated with congenital ureteropelvic junction obstruction (UPJO) and the relationship to clinical imaging have not been well studied. In order to better understand the histologic alterations of congenital UPJO and their relationship with clinical imaging and outcomes, we examined renal biopsies from 61 patients undergoing pyeloplasty for congenital UPJO. Glomeruli were analyzed for various injury patterns and the tubulointerstitium was examined for tubular atrophy/simplification and fibrosis. Two methods were used to evaluate tubular mass: glomerular density and morphometric measurement of tubular size and density. Control specimens were obtained from age-matched autopsy specimens without renal pathology. Glomerular changes were identified in 73% of all biopsies and were present in a range from 1.7 to 91% of glomeruli in each patient. Overt tubulointerstitial changes were present in 26% of all biopsies. Fibrosis was noted to occur with tubulointerstitial changes in a significantly greater fraction of children over the age of 1 year (P=0.026). Increased glomerular density was associated with severe hydronephrosis (P45%), postoperative functional decline was predicted only by increased glomerular density. 20 biopsies without overt tubulointerstitial changes were analyzed morphometrically and showed a significant reduction in proximal tubular (PT) size, but unchanged density. Distal tubular (DT) size was unchanged in UPJO, but density was increased. The PT/DT ratio was therefore markedly decreased in UPJO (P0.5 mm and this was associated with greater degrees of tubulointerstitial changes and glomerular alterations. Congenital UPJO produces a variety of renal parenchymal changes, which may in part reflect abnormal development. Some of these alternations are seen in clinical imaging and may help predict outcomes, but there is significant discordance between conventional imaging and histological findings.

The incidence of trypanosome infection was monitored in dairy cattle during a 6-month trial in Busia and Teso districts, western Kenya, to assess the efficacy of insecticide-treated netting for protection against tsetse flies. Frequently, the fragile netting did not last longer than 2 months because of destruction by strong wind or animal movements. Also, many farmers let their cattle graze freely outside the units during the day, despite technical advice, resulting in exposure of the free-ranging animals to habitats suitable for tsetse and thereby an increased risk of trypanosome infections. The trial groups thus comprised 34 animals from 11 dairy units that were continuously protected, and 153 animals from 46 dairy units that were partially protected. The control group consisted of 162 animals in 42 unprotected units. The phase-contrast buffy-coat technique was used for parasitological monitoring. The mean hazard rate for trypanosomes was significantly lower in protected cows, with a value of 0.007 as opposed to 0.02 for the control animals. Mean packed cell volumes (PCV) were significantly higher in protected cattle (29.7%) than in unprotected ones (27.6%). Farmers with protected animals also reported fewer nuisance flies and mosquitoes in their compounds.

SummaryInterleukin (IL)-16 is involved in the regulation of the expression of several proinflammatory cytokines, i.e. tumour necrosis factor (TNF)α and interleukin (IL)-1β. The present study aimed to determine the prevalence of the −295 promoter polymorphism of the interleukin (IL)-16 gene in periodontal disease. A total of 123 patients with periodontal disease and 122 healthy controls were genotyped for the −295 IL-16 promoter polymorphism. Genotyping has been performed by PCR and restriction fragment length polymorphism (RFLP) analysis. The frequencies of alleles and genotypes as well of haplotypes within both study groups were compared using the Pearson χ2 test at a level of significance of 5% (P

We examined the mechanisms responsible for technical failure of the endoscopic technique for correcting vesicoureteral reflux based on endoscopic anatomy.The study included 25 patients, 2 to 15 years old (mean age 8) who received 57 ureteral injections on 1 or more occasions which failed to correct reflux. Each endoscopic procedure for every patient was videotaped and endoscopic photographs were taken to document pretreatment and posttreatment anatomy. Based on the comparative endoscopic anatomical findings, failures were categorized as secondary to volume loss, mound displacement, mound extrusion or indeterminate etiology.Of the 57 ureters the cause of failure was believed to be due to mound displacement in 35%, volume loss in 23%, displacement and volume loss in 29%, mound extrusion in 2% and indeterminate in 11%. The direction of mound displacement was toward the bladder neck (medial, distal) in 76% of those cases.Endoscopic anatomical findings can account for failure of the injection technique to correct reflux in the majority of failed cases (90%). Mound displacement and volume loss account comparably for treatment failure. One incidence of mound extrusion, previously hypothesized as a mechanism for treatment failure, was documented in our study.

The overactive bladder (OAB) in children is defined as both involuntary detrusor contractions and urethral instability. The development of urinary control plays a key role in its incidence and in our understanding of its pathogenesis. It is seen in a number of conditions but by far is most common among patients with dysfunctional voiding. Urinary infection can be both a cause and an effect of OAB. In some instances, vesicoureteral reflux may result from detrusor overactivity because its successful resolution has been shown to depend on abolition of the hyperactivity. Early diagnosis and appropriate treatment can affect upper urinary tract function and drainage and ultimate bladder function. Recognition is noted via a thorough history and careful physical examination. Urodynamic assessment is indicated in neurologically normal children >5 years old and is combined with a voiding cystourethrogram in boys and a radionuclide cystogram in girls who have a history of recurrent urinary infection. Treatment consists of prophylactic use of anticholinergic agents in patients with neurologic dysfunction, as an early adjunctive measure in boys after ablation of posterior urethral valves, and in children with vesicoureteral reflux. The dose must be carefully titrated in children with cerebral palsy to prevent the appearance of elevated residual urine. Behavioral therapy and biofeedback techniques are effective alternatives to anticholinergic agents for children with dysfunctional voiding.

Summary Objective This pilot study evaluated the safety, feasibility, and usefulness of the Self-Cathing Experience Journal (SC-EJ), an online resource for patients and families to address issues and stigma surrounding clean intermittent catheterization (CIC). Modeled after previous assessments of the Cardiac and Depression Experience Journals (EJs), this project uniquely included patients and caregivers. We explored whether patients and caregivers would find the SC-EJ helpful in increasing their understanding of CIC, accepting the medical benefits of self-catheterization, improving hopefulness, and diminishing social isolation. Methods Patients seen in a tertiary urology clinic were asked to view the SC-EJ for 30 min and rate its safety and efficacy. The cross-sectional sample included 25 families: 17 surveys were completed by the patient and their caregiver, five by the patient only, and three by the caregiver only. Mean patient age was 15.7 ± 5.8 years (range 7–29 years). The patients were 64% female, and 72% used CIC due to neurological diagnoses. Results Mean overall patient satisfaction with the SC-EJ was moderately high (mean = 5, out of a 7-point Likert scale from 1 = not at all to 7 = extremely). Mean overall caregiver satisfaction was high (mean = 5.55) and was similar to caregiver satisfaction scores recorded in caregivers with children with congenital heart disease and depression (mean = 5.7 and mean = 5.75, respectively). No significant differences were noted in satisfaction between CIC patients and CIC caregivers or among caregivers of the three populations surveyed (CIC, Cardiac, and Depression). CIC patients and caregivers reported that SC-EJ viewing gave them a strong sense that others are facing similar issues (patient mean = 6.15, caregiver mean = 6.21) and that it was helpful to read about other families' CIC experiences (patient mean = 6, caregiver mean = 5.89). Discussion The SC-EJ appears to be safe, feasible, and useful to patients and families using CIC. Ratings from caregivers of CIC patients were similar to other cohorts of caregivers facing chronic childhood conditions. Despite beliefs that the EJ format best targets adults, high satisfaction ratings among patients suggest that the SC-EJ is acceptable and beneficial to children and adolescents. This web-based intervention can be a helpful clinical supplement in promoting healthy coping skills and a decreased sense of isolation among patients and families facing CIC. The unique integration of real patient and family experiences with accurate and vetted medical knowledge has the potential to enhance resiliency among viewers who use CIC. Table . Mean ratings and SDs for satisfaction and safety of the Self-Cathing Experience Journal by patients and caregivers and comparison of caregiver ratings from the cardiac and depression experience journals. a Patients using CIC ( n = 22) Caregivers of patients using CIC ( n = 20) Mothers of patients with cardiac disease ( n = 40) Caregivers of patients with depression ( n = 35) Comparison of CIC patients and caregivers ( p ) Comparison of caregivers (CIC, cardiac, depression) ( p ) Overall, how satisfied are you with the Self-Cathing Experience Journal? 5 ± 1.17 5.55 ± 1.15 5.7 ± 1.8 5.75 ± 1.66 0.1329 0.9070 Did you feel that the Self-Cathing Experience Journal was hurtful? 1.15 ± 0.37 1.35 ± 1.35 1.2 ± 0.7 1.43 ± 1.14 0.5076 0.6219 Did the Self-Cathing Experience Journal give you any sense that there are others facing similar issues? 6.15 ± 1.18 6.21 ± 1.08 6.7 ± 0.7 6.44 ± 0.91 0.8648 0.1103 Did you find it helpful to read about and see other families' experiences? 6 ± 1.20 5.89 ± 1.24 5.7 ± 1.5 6.06 ± 1.39 0.7718 0.5449 Did the Self-Cathing Experience Journal increase your sense of hope? 4.95 ± 1.70 5.11 ± 1.76 5.1 ± 1.9 5.44 ± 1.42 0.7661 0.6518 CIC = clean intermittent catheterization, used in self-catheterization. a Based on 1–7 Likert scale (1 = not at all, 4 = moderate, 7 = extremely).

The objective of this document created by the ICCS standardization subcommittee is to provide a uniform guideline on measurement, quality control and documentation of urodynamic studies in children.This guideline was created using expert opinion and critical review of the published literature on urodynamic studies in children. Currently no standardized guideline or level 1 data exists on the proper technique for this subject matter.The document provides a throughout explanation on how to approach a child who presents with lower urinary tract dysfunction, whether it be of neurogenic, anatomic or functional origin. Formation of an urodynamic question after a comprehensive history and physical examination is paramount in selecting the urodynamic study(ies) that will be most appropriate for each child. Appropriate application of each test with careful consideration of the needs of the child and family will provide the most accurate and reproducible results. Recommendations on how to execute each of the components of an urodynamic study as well as interpretation are included in the document.Urodynamic studies have become a major tool in evaluating lower urinary tract dysfunction in children. There are many subtleties in performing these studies in children in juxtaposition to adults; therefore, adaptations specific to children must be made to achieve accurate and reproducible results. Uniformity in how the studies are conducted from center to center will allow for healthier transparency and enhanced comparison of results in both clinical and research situations.

The split spinal cord malformation (SSCM) is an occult spinal dysraphism which causes tethering of the spinal cord. We performed a retrospective analysis of 15 patients who had split cord malformations (without associated open neural tube defect) who underwent both pre- and postoperative urodynamic studies (UDS) in order to determine if a significant percentage of these patients, even in the absence of overt urologic symptoms, had evidence of urologic dysfunction. Eleven patients presenting in early childhood and 4 patients presenting later in life are reviewed. Despite the lack of preoperative urologic symptoms in almost all patients, 73% of patients had voiding abnormalities on formal testing. UDS on these patients before and after surgery was a useful adjunct to perioperative management and decision making, helped define the success of surgery, and gave objective information for cases in which retethering was suspected.

High pressure dyssynergic voiding may result in irreversible damage to the urinary tract. Prophylactic therapy in the form of clean intermittent catheterization and anticholinergic medication may significantly decrease the incidence of upper urinary tract deterioration. Whether prophylactic therapy in the high risk bladder may also lead to improved long-term bladder dynamics prompted us to study the effect of early versus late treatment of bladder hypertonicity and detrusor-sphincter dyssynergia on the ultimate need for bladder augmentation.We retrospectively reviewed urological outcomes in patients with myelodysplasia who were at risk for urological deterioration within year 1 of life based on bladder sphincter dyssynergia and/or high filling or voiding pressure. We recorded the dates when high risk voiding dynamics were initially observed, and when intermittent catheterization and anticholinergic therapy were initiated. Patients in whom treatment began at the time a high risk profile was noted (prophylactic group seen between 1985 and 1990) were compared to controls with the same high risk voiding parameters who did not receive early therapy (observation group seen between 1978 and 1984 with therapy instituted 1 year or longer after high risk was noted). The number of augmentations performed in each group was indexed to the total number of years of followup in the 2 populations, respectively. Patients with less than 2 years of followup were excluded from further analysis.Of the 45 patients at risk clean intermittent catheterization and anticholinergic medication were immediately initiated in 18, while 27 were treated expectantly. Patients in the observation group were followed an average of 4.1 years (range 1.1 to 14) before clean intermittent catheterization and anticholinergic medication were started. Of the 27 children treated expectantly 11 (41%) required augmentation, whereas only 3 of the 18 (17%) treated prophylactically required enterocystoplasty. When the number of augmentations was indexed to total years of followup in each of the 2 groups (296 versus 156 years) patients in the expectant group were nearly twice as likely to require augmentation.Identification and early proactive treatment of the high pressure, dyssynergic lower urinary tract significantly decreases the need for bladder augmentation as children with neurogenic bladder secondary to myelomeningocele mature.

In order to investigate to what extent various determinants in the decision-making process for the treatment of severely ill incompetent patients are influenced by cultural and sociopolitical factors, 540 physicians in Austria, Germany (East and West), and Sweden, countries representing different healthcare systems, were surveyed using a self-administered questionnaire. It provided three case vignettes with different levels of information about the patient's treatment wishes in case of incompetence in a life-threatening situation. We found a general trend to a lower level of treatment in line with the patient's wishes when the information provided was more detailed. Remarkably, a substantial number of doctors did not comply with the patient's wishes. Ethical concerns and patient's wishes appeared as the most important factors whereas religious beliefs of the physician and hospital costs scored lowest. Because of the variability of treatment decisions and the importance of various factors determining the decision-making, an advance directive may be a feasible way of reducing the number of conflicts in critical situations. We recommend that ethical issues of clinical practice should be emphasized in the medical curriculum and in the training of physicians.

The disruption of the endocrine systems of gastropod molluscs and consequential physiological changes (imposex and intersex) are used as biomarkers for environmental contamination by tributyltin compounds. The first international laboratory performance study on the determination of imposex and intersex in neogastropod molluscs, Nucella lapillus and Littorina littorea has been undertaken by the QUASIMEME (Quality Assurance of Information for Marine Environmental Monitoring in Europe) project. Samples of live gastropods were distributed and participants were asked to record shell height and sex, together with penis length and vas deferens sequence stage (VDS) in Nucella or the intersex stage (IS) and prostate length in Littorina. Calculations were made of vas deferens sequence index (VDSI) and the relative penis size index (RPSI) in Nucella and of intersex stage index (ISI) and the average female prostate length (FPrL) in Littorina. Thirteen (87%) of the 15 participating laboratories returned data. The remaining two laboratories asked to participate in later exercises. For Nucella, seven laboratories reported sex ratios significantly different from the reference laboratory data. Differences in penis length measurements between laboratories were largely random, although there were indications of systematic errors affecting the data from three laboratories. Seven laboratories reported satisfactory data (Z-score magnitude of Z < 2) for VDSI. The inclusion of a high proportion of sub-adults in the Nucella samples may have made separation of the sexes more difficult than in mature adults. The sub-adults will have had smaller pene than mature adults in the same population, and therefore any errors (random or systematic) in the measurement of penis length or observation of reproductive organs would have a potentially greater impact on the final reported values of the summary imposex indices. The Littorina sample did not show a high degree of intersex (ISI = 0.41). The laboratories could determine the sex of Littorina reliably and only one laboratory reported data significantly different from the reference laboratory. All except two laboratories reported satisfactory data for ISI.

Drug-induced headache is a well-known complication of the treatment of primary headache disorders, and its successful management is only possible by withdrawal therapy. However, it is unknown whether ambulatory or stationary withdrawal is the therapy preferred. We conducted a prospective study on the outcome of stationary versus ambulatory withdrawal therapy in patients with drug-induced headache according to the International Headache Society criteria. Out of 257 patients with the diagnosis of drug-induced headache during the study period, 101 patients (41 after ambulatory and 60 after stationary withdrawal therapy) could be followed up for 5.9 ± 4.0 years. The total relapse rate after successful withdrawal therapy was 20.8% (14.6% after ambulatory and 25.0% after stationary withdrawal therapy, p

The aim of the study was to identify the most appropriate dosage combination of ramipril and felodipine ER (an extended release tablet) for mild-to-moderate hypertension. Hypertensive patients (N = 507) with supinediastolic blood pressure (DBP) values between 100-115 mm Hg were included in a randomized, multicenter, double-blind study of 3x4 factorial design with a 2-4 week single-blind, placebo run-in and 6 week active treatment phase. The patients were randomized to 12 groups: placebo, ramipril (2.5, 5, 10 mg), felodipine ER (5, 10 mg), or ramipril-felodipine ER combinations (2.5/5 mg, 2.5/10 mg, 5/5 mg, 5/10 mg, 10/5 mg, 10/10 mg). Although the greatest reductions in blood pressure were observed with ramipril-felodipine ER (10/10 mg), consideration of the antihypertensive efficacy and safety factors suggest that the ramipril-felodipine ER (5/5 mg) combination has the best efficacy/tolerability ratio of the combinations tested. The incidence of adverse events with ramipril-felodipine ER combination therapy was similar to that with felodipine ER monotherapy, but peripheral edema, tachycardia and vasodilatation occurred less frequently with ramipril-felodipine ER (5/5 mg) combination than with felodipine ER monotherapy. The combination of ramipril-felodipine ER (5/5 mg) can be considered to be the most suitable option for hypertensive patients with an inadequate response to either of the monocomponents.

There is strong evidence for a loss of habituation during cognitive processing in migraine as measured by P300 and contingent negative variation in adults. Event-related potentials evoked by an oddball paradigm have not yet been studied in children and adolescents suffering from different primary headache types. We recorded visually evoked event-related potentials (two consecutive trials, 200 stimuli each) in 48 children and adolescents suffering from migraine without or with aura, from episodic tension-type headache, and from ergotamine-induced headache and analyzed the latencies, amplitudes, and reaction times. No statistically significant differences were noted between all headache types and healthy controls analyzing the averaged parameters for the whole measurement. However, a highly significant loss of cortical habituation as measured by P300 amplitude and latency could be observed in migraine without and with aura by analyzing the first and the second trial of measurement separately. This phenomenon increased with age and could not be seen in healthy controls, or patients with tension-type headache or ergotamine-induced headache. Our data suggest a specific cognitive processing in migraine even in children and adolescents. Measurement of the habituation effect in P300 latency and amplitude provides a specific method to differentiate between primary headache types in childhood and adolescence. (J Child Neurol 1998;13:322-326).

An accurate estimation of normal bladder capacity can be helpful in evaluating the patient with genitourinary disease and in interpreting urodynamic data. Prior studies have provided initial estimates. We propose 2 new equations that are practical, easy to use and more accurate than those previously published.We retrospectively reviewed the records of more than 5,000 children undergoing radionuclide cystography at our institution. Radionuclide cystography was conducted by instilling (99m)technetium pertechnetate via gravity drip in awake children. Bladder capacity was believed to be achieved when rate of inflow diminished to a minimal rate, initiation of voiding occurred or significant discomfort was indicated. Patients with vesicoureteral reflux, infravesical obstruction, urinary tract infection, dysfunctional voiding or other lower urinary tract pathology were excluded from the study. Linear and nonlinear regression modeling established the relationship between age and bladder capacity.A total of 2,066 children (598 boys and 1,468 girls) had normal radionuclide cystography and were included in the analysis. Analysis of variance demonstrated that increasing age was strongly predictive of bladder capacity (p0.0001). Because a nonlinear model was the most accurate formula for all ages (4.5 x age(0.40) = capacity [ounces]), 2 practical linear equations were determined: 2 x age (years) + 2 = capacity (ounces) for children less than 2 years old, and age (years) divided by 2 + 6 = capacity (ounces) for those 2 years old or older. Although girls had larger capacities than boys, the rate of increase was not significantly different between them.The relationship between normal bladder capacity and age in children follows a nonlinear curve. This nonlinear relationship can be approximated by 2 practical linear formulas that are easy to remember and are derived from a larger population than any prior study. These formulas provided accurate estimations of bladder capacity when prospectively applied to normal patients.

Determining the role of the bladder in incontinence and/or upper urinary tract deterioration involves the cystometrographic evaluation of detrusor compliance. Management decisions based on information provided by standard fill water cystometry assume that data reflect the physiological state of the patient but this is not always true. We report the use of pressure at residual volume as a physiological measurement to aid in the interpretation of data obtained during standard fill urodynamics.All patients presenting to our urodynamic suite for standard cystometry between June 1994 and December 1995 underwent measurement of bladder pressure at insertion of the urodynamic catheter. Residual volume and pressure measured before draining this urine, that is pressure at residual volume, were recorded. The bladder was then filled at a rate equal to or less than 10% per minute of known or predicted capacity. When a volume equal to the residual volume had been instilled, filling pressure was recorded and the remainder of the standard urodynamic evaluation was completed. Uncooperative patients as well as those with an active infection or residual volume less than 10 ml. were excluded from further analysis.In 152 children pressure at residual volume was compared to filling pressure and the difference was analyzed. Filling pressure was higher than pressure at residual volume in the majority of cases. In 59 children there was a positive change (filling pressure greater than pressure at residual volume) of 5 cm. water or greater and in 13 there was a negative change (pressure at residual volume greater than filling pressure) of 5 cm. water or less. When only cases in which pressure at residual volume was greater than 5 cm. water were analyzed, 46 and 33% had a difference between filling pressure and pressure at residual volume of 5 cm. water or greater and 10 cm. water or greater, respectively.Pressure at residual volume is physiological, simple to determine and may provide additional information regarding storage characteristics of the bladder. In the context of the clinical history differences between pressure at residual volume and filling pressure may help to interpret standard fill cystometry data.

We attempted to determine the incidence of vesicoureteral reflux in asymptomatic siblings of children with reflux at different ages and assess the incidence of renal damage in asymptomatic siblings with reflux.We reviewed radionuclide cystograms of 482 consecutively referred siblings of children with vesicoureteral reflux, including 295 girls and 187 boys 2 weeks to 12.8 years old (mean age 2.8 years). Ultrasonograms and renal cortical scintigrams of children with reflux were evaluated. All siblings were considered asymptomatic by the referring physicians.The overall incidence of vesicoureteral reflux was 36.5%, and the incidence in girls and boys was 39.3 and 32.1%, respectively. Children 24 months old or younger had the highest incidence (45.7%) and the highest risk of bilateral reflux. From ages 25 to 72 months the incidence of reflux was 33.1% and in siblings older than 72 months it was 7%. Reflux of urine to the level of the renal pelvis was detected in 28.6% of all referred siblings. Renal damage was observed on sonography or scintigraphy in 4.7% of the siblings with reflux.The high incidence of vesicoureteral reflux through age 72 months indicates that it is important to screen siblings of children with reflux at an early age to prevent renal damage, which can occur in the absence of symptomatic urinary tract infection.

We attempted to assess the usefulness of urodynamic testing for diagnosing lipoma and lipomeningocele, and the late effects of early neurosurgical intervention in children less than 1 year old.A total of 28 patients in whom spinal surgery was performed before age 1 year for correcting lipoma and lipomeningocele underwent neurological and urodynamic evaluation preoperatively, and within 3 months and up to 14.5 years postoperatively.Preoperatively 15 patients (54%) had an abnormal neurological examination and 7 had an abnormal urodynamic study. Of the 13 patients with a normal neurological examination 3 had an abnormal urodynamic study. Overall 10 patients (37%) had an abnormal urodynamic examination preoperatively. Immediately after surgery 8 patients (29%) had improvement (2 of 15 with an abnormal neurological examination and 6 of 10 with an abnormal urodynamic study), whereas the condition of 9 (32%) worsened, including 4 of the 13 who were neurologically and 6 of the 18 who were urodynamically normal (1 in both categories). With time an additional 7 patients (25%) had progressive deterioration, including 6 urodynamically and 5 neurologically (4 in both categories), 2 (7%) had improvement (1 each urodynamically and neurologically) and the condition of 19 (68%) remained stable. Six patients (21%) underwent secondary spinal surgery for recurrent tethering.Early surgical repair seems to provide a degree of protection against later spinal cord tethering, and subsequent neurological and/or urodynamic deterioration (25% of our patients versus a reported 80% of those followed expectantly).

Centenarians born 1887–91, who lived in southern Sweden were asked to participate in this multidisciplinary study ( N = 164). Of the survivors ( N = 143), 70 percent agreed ( N = 100). The purpose was to describe the population from physical, social, and psychological points of view; to characterize centenarians with various health conditions and diverse degrees of autonomy and life satisfaction; and to identify factors at 100 years that predict future survival. Results: Eighty-two percent were women, 25 percent lived in their own home, 37 percent in old age homes, and 38 percent in nursing homes. Socioeconomic status showed a similar distribution compared to nationally representative data. Fifty-two percent managed activities of daily living with or without minor assistance. The incidence of severe diseases was low. In 39 percent a disorder of the circulatory system was found. Thirty-nine percent (women) and 11 percent (men) had had at least one hip fracture. Twenty percent had good hearing and good vision. Twenty-seven percent were demented according to DSM III-R criteria. Means on cognitive tests (word-list, digit-span, learning, and memory) were lower compared to seventy to eighty year old groups. The variation in performance was extremely widespread. Personality profiles (MMPI) indicated that the centenarians were more responsible, capable, easygoing and less prone to anxiety than the population in general. Extensive neuropathological investigation revealed no major diseases or large lesions but mild though multiple changes. Results suggest that centenarians are a special group genetically. A causal structure model emphasized body constitution, marital status, cognition and blood pressure as particularly important determinants for survival after 100 years.

IN this issue of The Journal 2 articles provide a cogent argument for classifying lower urinary tract function in children with bladder and bowel dysfunction. Fast et al (page 1028) retrospectively evaluated children referred with lower urinary tract symptoms (LUTS) and placed them into specific dysfunction categories they developed. 1‐3 They simultaneously examined bowel elimination status using several criteria (Rome III classification; stool burden on plain x-ray of the kidneys, ureters and bladder; voiding diaries that included bowel emptying and rectal ultrasonography) to diagnose fecal incontinence and/or retention, as well as the association with a specific classification of LUTS. Combs et al (page 1015) categorized a group of children referred with reflux and apparent LUTS in their classification schema, 4 and then used targeted treatment to see if the resolution rates of reflux were positively affected compared to historical controls of antibiotic therapy alone. 5 These groups attempted to make a logical argument for the careful analysis of children with bladder and bowel dysfunction to gain an understanding of what may be wrong with their lower urinary and gastrointestinal systems, and how best to manage them and any associated conditions (ie vesicoureteral reflux). Therefore, the authors created a urological classification system based mostly on noninvasive urodynamics and selected cystometrography (when used simultaneously with video cystography). They suggested that children with abnormal bladder and bowel elimination habits as well as those with reflux seem to display a spectrum of conditions that require identification so specific management options can be used to improve the clinical outcome. It has been demonstrated that symptoms alone may not be sufficiently accurate to classify cases in specific categories and that urodynamic testing alone is also imperfect in comparing findings to symptoms. 6 In its standardization document on daytime incontinence the International Children’s Continence Society has shown the value of flow rates with and without electromyography with patch electrodes to differentiate the etiology of an intermittent emptying pattern. 7 In cases of ambiguity, urodynamic testing provides a means of separating organic from functional causes for lower urinary tract dysfunction. Thus, a combination of careful history taking and patient oriented diary entries along with the judicious use of investigational studies should provide a reasonable picture of the pathology. As clinicians, with these tools we may then be able to come up with a system that allows for a better understanding of underlying conditions such as reflux

We examined data from multiple institutions to determine whether intravesical bladder stimulation therapy is effective in improving bladder compliance by increasing bladder capacity and lowering bladder storage pressures.The charts of 568 patients from 11 institutions were evaluated. Of the 568 patients 335 had adequate and accurate pretreatment and posttreatment urodynamic studies, and were included in this study. A total of 155 patients was from Children's Memorial Hospital, while the remaining 180 were from 10 other institutions. Bladder capacity and bladder capacity pressure were determined for each patient before and after therapy.Overall, 53% of patients had increased bladder capacity of 20% or greater after treatment (average increase 105 cc), which represents a 63% increase from pretreatment values. This increase occurred in an average of 1.9 years. Further analysis of this subset of patients revealed that in 90% intravesical storage pressures were decreased or maintained within a safe range (less than 40 cm. water). Evaluation of patients who did not respond to bladder stimulation with a 20% or greater increase in bladder capacity revealed that they had nearly normal bladder capacity before therapy. When the data on bladder capacity and bladder capacity pressure from Children's Memorial Hospital were compared to results from the 10 other institutions, there were no appreciable differences.Bladder stimulation is effective in increasing bladder capacity without significantly elevating storage pressure in a majority of patients. We conclude that this technique is safe and effective in improving bladder compliance, and that it is reproducible elsewhere.

To assess the efficacy of the artificial urinary sphincter survival and continence were first evaluated 5 years ago. We now evaluated the effects of the artificial urinary sphincter more than a decade after implantation.Before 1985 an artificial urinary sphincter was implanted in 22 male and 14 female consecutive patients 4 to 30 years old (median age 12). In addition, between 1985 and 1990, 18 other children underwent artificial urinary sphincter implantation. Results of both series were compared.Of the 25 sphincters in the original series that were functioning after 5 years 1 was removed and 2 patients were lost to followup, resulting in 22 functioning implants (61% of the patients). Mean survival time of the prostheses was 12.1 years and average followup for functioning sphincters was 13.7 years. There was no statistically significant difference in artificial urinary sphincter survival between the original group at 5 years and the second group treated after 1985. Of the patients in both groups with sphincters in place 32 of 39 (82%) were dry. Augmentation cystoplasty was performed in 9 of 18 patients (50%) in the second series (5 preoperatively and 4 postoperatively) compared to 10 of 36 (28%) in the original series at 5 years (3 preoperatively and 7 postoperatively). Renal failure developed in 6 patients from both series.The artificial urinary sphincter is a durable long-term solution for children with intractable incontinence. Long-term surveillance of the urinary tract is mandatory because of the potential for renal failure in patients who have bladder hypertonicity after placement of the device.

A multinational, double-blind, randomised study was conducted to investigate the efficacy and safety of a low-dose combination of the angiotensin converting enzyme inhibitor, ramipril, and the calcium antagonist, felodipine ER, in 642 patients with mild to moderate hypertension [supine diastolic blood pressure (DBP) = 95-115 mm Hg]. After a 4-week single-blind placebo run-in, patients were randomly allocated to once-daily felodipine extended release (ER; 2.5 mg), ramipril (2.5 mg) or felodipine ER/ramipril (2.5/2.5 mg) for 12 weeks. In the intention-to-treat analysis, mean DBP decreased significantly (p0.0001) after felodipine ER, ramipril and the combination (-9.1, -9.8 and -11.4 mm Hg, respectively). The decrease was significantly greater with the combination than with felodipine ER monotherapy (p = 0.02). The number of responding patients (final DBPor = 90 mm Hg or a decrease ofor = 10 mm Hg) was also higher with the combination than with felodipine ER or ramipril monotherapy (65.1%, 53.1%, 55.7%, respectively). There were no differences between the three groups with respect to the incidence of adverse events overall or those considered treatment-related. There were fewer cases of peripheral oedema with combination therapy than with felodipine ER monotherapy. Thirty-three patients (5.1%) withdrew from the study because of adverse events, but there was no clear pattern with regard to the specific events leading to withdrawal. There were no clinically relevant changes in laboratory or clinical safety variables. Ramipril/felodipine ER 2.5/2.5 mg is an appropriate starting dosage when initiating combination antihypertensive therapy.