Four-hour voiding observations detect neurogenic lower urinary tract dysfunction in neonates with anorectal malformation.

INTRODUCTION: Neurogenic lower urinary tract dysfunction (LUTD) has been reported in 20-50% of children with anorectal malformations (ARM). As neurogenic LUTD represents an inherent risk of renal deterioration and urinary tract infections, an early diagnosis is important. The gold standard for evaluating neurogenic LUTD involves invasive urodynamic testing but a useful addition should be an easy-to-perform, non-invasive method of screening. OBJECTIVE: In this study, we evaluate non-invasive 4 h voiding observations as a screening method for neurogenic LUTD in ARM children. STUDY DESIGN: Thirty-four patients with ARM, excluding those with perineal fistulas, were evaluated using both 4 h voiding observation and urodynamic testing before and after posterior sagittal anorectoplasty (PSARP) at median ages of 0.3 and 1.1 years. In the urodynamic assessment, the gold standard for neurogenic LUTD, nine children received the diagnosis, eight innate and one post-surgery. RESULTS: Five boys with a high urethral fistula and anomalies of the spinal cord had urodynamically diagnosed neurogenic LUTD, a dysfunction also identified in the 4 h voiding observations. The pattern was characterised both by an increase in the number of voiding and the number of interrupted voiding, urinary leakage and elevated residual urine (Figure). In three girls with a vestibular fistula and tethered cord, an urodynamic investigation identified suspected mild neurogenic LUTD. In the voiding observations, an abnormal voiding pattern was not as obvious in the girls as in the five males. One girl with cloaca showed signs of postsurgical denervation damage, which was easily identified in the 4 h voiding observations (high capacity and elevated residual urine). DISCUSSION: In the present study, gender differences in the severity of dysfunction reflected in the free voiding pattern in infants with ARM and neurogenic LUTD is probably the result of the different underlying causes of neurogenic LUTD in boys and girls. Boys with the condition have a congenital malformation of the caudal part of the spinal cord and girls a tethering of the cord. The most obvious limitation of the study was the low number of patients. Despite this, we consider the results worth reporting, since we found that results in the free voiding observations effectively confirmed what was established in the urodynamic investigations. CONCLUSION: In pre-PSARP patients, 4 h voiding observations can be used to screen for severe neurogenic LUTD requiring attention and treatment. When post-surgical denervation is suspected, the voiding observation is also a good method for indicating the diagnosis.

A substance P antagonist, [D-Pro2, D-Trp7,9]SP, inhibits inflammatory responses in the rabbit eye.

Neurogenic factors released by antidromic nerve stimulation are thought to be in part responsible for the vasodilation and breakdown of the blood-aqueous barrier that follows trauma to the eye. Substance P is one candidate for the mediation of the inflammatory response since it is thought to be a neurotransmitter in sensory afferents and since exogenous substance P is capable of eliciting a response characteristic of inflammation. In rabbits, intravitreal or topical application onto the eye of a specific substance P antagonist, [d-Pro2, D-Trp7,9]SP, inhibited not only the irritant effects of exogenous substance P but also the inflammatory response to a standardized trauma (infrared irradiation of the iris). These observations suggest that substance P, or a related peptide, is a neurogenic mediator of the inflammatory response in the eye.

Fertility and pregnancy outcome in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

BACKGROUND: Low pregnancy rate has been reported in women with congenital adrenal hyperplasia (CAH) and little information on pregnancy and children is known. METHODS: In a Swedish study, 62 adult women with CAH, aged 18-63 years, and 62 age-matched controls were followed-up. Medical records, including those concerning pregnancies and deliveries, were examined and the 21-hydroxylase genotype of patients was noted. All women answered a questionnaire concerning sexual and reproductive health including health of the children. RESULTS: Pregnancy and delivery rates were significantly lower in women with CAH (P < 0.001, P < 0.0056, respectively), and the severity of the 21-hydroxylase-mutation correlated with the reduced number of children born. More women with salt-wasting CAH were single and had not attempted pregnancy. Pregnancies were normal except for a significantly increased incidence of gestational diabetes in CAH patients (P < 0.0024). The children had normal birthweight and no malformations were observed. A later follow-up of the children showed a normal intellectual and social development. The sex ratio of the offspring differed significantly, with 25% boys in the CAH group compared with 56% among controls (P < 0.016). CAH women had more gynaecological morbidity during menopause. CONCLUSIONS: Pregnancy and delivery rates are reduced in women with CAH mainly due to psychosocial reasons. The outcome of children did not differ from controls. The unexpected sex ratio in children born to mothers with CAH warrants further research.

The Swedish Infant High-grade Reflux Trial - Bladder function.

INTRODUCTION: It has been suggested that infants with high-grade vesicoureteral reflux (VUR) have lower urinary tract dysfunction (LUTD) that is characterised by large bladder capacity (BC) and increased post-void residual (PVR). However, most of these infants have normal or small BC in early infancy and develop large capacity during the first year of life. OBJECTIVE: This study aimed to see whether LUTD development during the infant years in children with high-grade VUR could be prevented by early reflux resolution. MATERIALS AND METHODS: For early VUR intervention, endoscopic treatment (ET) was used in a randomised trial comprising 77 infants (55 boys) aged <8 months with VUR grade 4-5 (n = 30/n = 47); 39 were randomised to antibiotic prophylaxis and 38 to ET. Voiding cystourethrogram, free voiding observation (FVO) and renal scintigraphy were performed at baseline and after 1 year. Bladder capacity and PVR were obtained from FVO. LUTD was defined as a BC of ≥150% of expected and a PVR of ≥20 ml. RESULTS: There were no differences in bladder function variables seen between the treatment groups, despite significant differences in VUR resolution. Analysing bladder function related to VUR outcome (VUR grade ≤2 vs grade >2), independent of treatment, showed that VUR grade ≤2 was associated with a smaller BC at 1 year (P = 0.050) (a tendency already seen at baseline) and a lower PVR at baseline (P = 0.010). PVR increased from baseline to 1 year (P = 0.037) in children with grade ≤2 VUR (Summary Table). The group with persistent bilateral grade 5 VUR at 1 year had more abnormal bladder variables compared with other study subjects, with a tendency of larger BC (P = 0.057), higher PVR (P = 0.0073) and more LUTD (P = 0.029) at baseline and a larger BC at 1 year (P = 0.016). In explanatory analyses, using logistic regression, a high PVR at baseline was identified as a predictor of VUR grade >2 (P = 0.046), persistent bilateral grade 5 VUR (P = 0.022), recurrent urinary tract infection (P = 0.034), and only a tendency was seen regarding new renal damage (P = 0.053). CONCLUSION: There was no between-group difference seen in bladder function. In children with VUR resolution at follow-up, independent of treatment, BC decreased, whereas PVR increased. High PVR at baseline was a predictive factor for both non-resolution of high-grade VUR and recurrent urinary tract infection. The results suggest that LUTD cannot be prevented by early VUR resolution, but rather is an important prognostic factor for VUR outcome in both endoscopic and prophylactic treatment.

Psychosocial outcome in adult men born with hypospadias.

INTRODUCTION: Hypospadias, which is a surgically treated congenital malformation of the male urethra, may have a negative impact on quality of life. This aspect has previously been subject to limited research. This study examined the long-term psychosocial outcome of a large cohort of adult males born with hypospadias. OBJECTIVE: The purpose of this case-control study was to assess a possible negative influence on the psychosocial outcome in adult males with hypospadias. STUDY DESIGN: Males with hypospadias treated in Sweden and aged ≥18 years old participated in this follow-up study. Age-matched men and university students were recruited as controls. The participants answered a questionnaire designed to reflect the subjective quality of life, social factors, need of support and follow-up, and the perceived impact of the disease upon upbringing. It also looked at the validated Psychological General Well-Being (PGWB) questionnaire and Relationship Questionnaire (RQ). RESULTS AND DISCUSSION: A total of 167 patients (median age 34 years, 63% distal, 24% mid, and 13% proximal hypospadias) and 169 controls (median age 33 years) participated in the study. Patients had their first operation at 4 years of age (median) and the median follow-up time was 29 years following the first surgery. Men with hypospadias had a comparable total quality of life level with a mean total PGWB score of 82 (normal range 78-83) compared with 85.6 in controls. Scores on wellbeing and vitality were lower, even if the differences were small. Hypospadias did not affect marital status, presence of children in the family, frequency of employment or experience of bullying. These men more often lived at home with their parents (P=0.001) and had a lower level of education (P=0.004), even if the educational level in both patients and controls was high compared with the general Swedish population. Patients with proximal hypospadias were shorter compared with controls (P=0.003), which was consistent with the prenatal growth restriction associated with hypospadias. The group with proximal hypospadias expressed a greater need for medical (45.5%) follow-up compared with mid (28.2%) and distal (18.1%) cases (P=0.001). Patients with proximal hypospadias tended to avoid close relationships because of fear of being hurt. CONCLUSIONS: The findings suggested that patients treated for hypospadias have a good HRQoL, can be expected to have a normal psychosocial life, and marry and have children. Repeated follow-up and psychological support during childhood/adolescence is however of great importance for patients with more proximal hypospadias.

Sexuality and fertility in men with hypospadias; improved outcome.

The aim of this study was to investigate sexual function and fertility in adult men born with hypospadias. Patients born with hypospadias, age-matched controls, and a group of circumcised men completed a questionnaire constructed to reflect their psychosexual situation and fertility. Core gender identity, sexual orientation, and gender role behavior was also assessed. 167 patients [63% distal, 24% mid shaft and 13% proximal, mean age 34 (19-54) years], 169 controls from the general population [mean age 33 (19-48) years] and 47 controls circumcised because of phimosis (mean age 26 [19-44]) participated and completed the questionnaire. There were no differences in having a partner, reported fertility, age at sexarche (mean age 17.8), number of sex partners or sexual interest between the patients and controls. More patients than controls reported anejaculation. Reported glanular sensitivity was lower in hypospadias patients and circumcised controls compared with non-circumcised controls. The odds of being satisfied with their sexual life increased with a higher penile perception score in patients (OR = 1.54, p = 0.01). There was no association with penile length. Sexual orientation, core gender identity and gender role behavior were sex-typical in both patients and controls. Patients with proximal hypospadias had a lower reported fertility, experienced anejaculation more often, and were less satisfied with their sexual life. Men born with hypospadias have a good long-term outcome concerning sexual function and fertility. Men born with proximal hypospadias have a more impaired outcome concerning both sexual function and fertility. As satisfaction with genital appearance is important for sexual life satisfaction, clinical, and psychological follow-up into adulthood is especially important in boys born with proximal hypospadias.

The effect of timolol maleate on the disruption of the blood-aqueous barrier in the rabbit eye.

A disruption of the blood-aqueous barrier in rabbit eyes was elicited by use of topical prostaglandin E2(PGE2), infrared irradiation of the iris, or by subcutaneous alpha-melanocyte-stimulating hormone (alpha-MSH). The aqueous flare provoked was measured quantitatively with a photoelectric instrument. The effect of the (topical) beta-adrenergic antagonist timolol maleate on the breakdown of the blood-aqueous barrier was tested. Timolol applied topically in very large doses had no effect on exogenously administered PGE2. However, even in a very small concentration applied topically, timolol reduced the flare response to both infrared irradiation and alpha-MSH. These results support the theory that the effect of alpha-MSH and infrared irradiation on the blood-aqueous barrier is dependent on intact beta-adrenergic receptor sites.

Bladder dysfunction in boys with posterior urethral valves.

UNLABELLED: Posterior urethral valve (PUV) is a congenital urethral obstruction affecting boys. As a result of the obstruction in fetal life, these boys often have a persisting bladder dysfunction, which is one of the main causes of the late onset renal failure seen in 1/3 of the boys and is also responsible for the delayed achievement of continence. The aim of this study was to characterize the bladder dysfunction from infancy through childhood and adolescence in boys with neonatally diagnosed PUV with the intention of designing a bladder treatment regimen starting in infancy. Paper I: 16 infant boys with PUV were followed with repeated standard cystometries. At presentation the bladders were hypercontractile with low capacity. During the first three years of life the urodynamic pattern changed, with vanishing hypercontractility and increasing bladder capacity, even though the instability remained unchanged. Paper II: 12 boys were followed with standard cystometries between 4 and 12 years of age and compared with a group of 6 postpubertal boys with PUV. The urodynamic pattern continued to change, with decreasing instability and contractility. A major problem was emptying difficulties. Paper III: The voiding pattern during the day versus the night in 10 incontinent and 6 continent boys with PUV was evaluated by long-term natural filling cystometry. The voiding pattern, with small frequent voidings during the day and few or no voidings during the night with high bladder volumes in the morning, could be explained by pronounced instability during the day whereas the bladders were stable during the night. Paper IV: The method of "4 hour voiding observation" was presented as a non-invasive method for basic assessment of bladder function in non-toilet trained children and the voiding pattern in 43 healthy infants was demonstrated. Paper V: The voiding pattern, with special attention to emptying difficulties, in 25 small children with PUV compared to healthy children of corresponding age, was evaluated with the "4 hour voiding observation." CONCLUSIONS: Boys with PUV have a bladder dysfunction with a changing urodynamic pattern over time with decreasing contractility and instability. In small boys the instability was pronounced during daytime while during the night the bladders were mainly stable. Most boys with PUV and bladder dysfunction end up with a deconpensated bladder. A major problem was bladder emptying difficulties. The "4 hour voiding observation" is an excellent non-invasive method of identifying those patients in need of early bladder treatment, i.e. with clean intermittent catheterisation.

Urinary bladder control during the first 3 years of life in healthy children in Vietnam--a comparison study with Swedish children.

OBJECTIVES: To study outcomes of early potty training in a population of healthy children with a tradition of early potty training and to compare these findings with a group of children to whom potty training was applied later. SUBJECTS AND METHODS: Mothers and their 47 healthy children in Vietnam participated in this longitudinal study. The voiding pattern and emptying ability were followed by the 4-h voiding observation method from 3 months to 3 years of age. A comparison is made with a group of 57 Swedish children investigated in a similar manner. RESULTS: In the group of Vietnamese children, 89% were on daily potty training at the age of 6 months. At the age of 24 months, potty training was complete for 98%. In the Swedish group, just a few (5%) had started daily potty training by the age of 24 months (p < 0.001). The Vietnamese group had fewer voidings and lower voided volumes than the Swedish group. In the Vietnamese children, bladder emptying could be regarded as having been completed, with no residual urine at 9 months, compared with the Swedish group, which first showed complete emptying at the age of 36 months. CONCLUSION: Potty training performed daily affects the emptying ability positively. In the Vietnamese group, no residual urine was found at the age of 9 months. These results differ significantly from those of the group of Swedish children.

Treatment of bladder dysfunction and high grade vesicoureteral reflux does not influence the spontaneous resolution rate.

PURPOSE: We investigated whether the treatment of bladder dysfunction in infants with congenital high grade vesicoureteral reflux could influence the spontaneous resolution rate of the reflux and the number of recurrent urinary tract infections. MATERIALS AND METHODS: A total of 115 infants with high grade vesicoureteral reflux were included in a followup study of bladder function and reflux resolution between 1993 and 1999. The present study deals with 20 of these infants with mainly grade V reflux, most of whom had recurrent urinary tract infections in combination with high post-void residual and high bladder capacity. Treatment with clean intermittent catheterization was instituted during infancy in these 20 patients and continued until a median age of 4 years. RESULTS: Bladder capacity was high at presentation and at all followup investigations in the clean intermittent catheterization treated group. Moreover, residual urine was high at presentation and especially between ages 1 and 2 years. However, after bladder control was achieved this residual decreased and consisted mainly of reflux urine. In only 1 girl did reflux resolve spontaneously during the 4-year followup period. A total of 18 patients were treated surgically at the end of this period, and clean intermittent catheterization could be stopped a few months later in all but 2. Urinary tract infection recurrences were uncommon after the institution of treatment. CONCLUSIONS: The treatment of bladder dysfunction characterized by a high capacity bladder with poor emptying in infants with congenital high grade reflux does not influence the rate of spontaneous resolution. On the other hand, the tendency toward recurrent urinary tract infections appears to decrease with treatment.

The voiding pattern in infants with dilating reflux.

OBJECTIVE: To determine whether the voiding pattern in infants with dilating vesico-ureteric reflux (VUR) differs from that in healthy infants, thus supporting the existence of bladder dysfunction in infants with VUR. PATIENTS AND METHODS: Forty-one infants (33 boys and eight girls) with dilating VUR (grades 3-5) were studied using a noninvasive 4-hourly voiding record described previously in studies of the voiding pattern of healthy infants, and the results compared with those obtained from healthy infants of similar age. RESULTS: The voiding pattern in the boys with VUR was characterized by small frequent voids and interrupted voids in more patients (36%) than in healthy boys (15%). Conversely, the girls with VUR were infrequent voiders of relatively high volumes. Residual urine was significantly increased in both boys and girls, as was bladder capacity, although not significantly. CONCLUSIONS: The free voiding pattern in infants with dilating reflux differs from that seen in healthy infants of comparable age. The characteristics for boys and girls differed but was in accordance with that seen in invasive urodynamic studies, suggesting refluxing infants to have a bladder dysfunction.

The changing urodynamic pattern in valve bladders during infancy.

Bladder dysfunction in boys with posterior urethral valves is well documented in studies of long-term followup. These reports suggest that dysfunctional bladders can be divided into 3 main types, including unstable, low compliant and over distended. To our knowledge urodynamic findings at presentation during infancy have not been described previously. We report on 16 male patients born between 1989 and 1993 who presented with symptoms of posterior urethral valves between birth and age 5 months, and who were followed with repeated urodynamic evaluations for a mean of 19 months. At presentation the bladder was hypercontractile with low capacity. During the first 3 years of life, the urodynamic pattern changed with vanishing hypercontractility and increasing bladder capacity, although instability remained unchanged with emptying difficulties. Thus, the 3 patterns of bladder dysfunction reported in older boys after resection of posterior urethral valves could not be found in infants and small children.

Bladder dysfunction in boys with posterior urethral valves before and after puberty.

PURPOSE: We characterized bladder dysfunction in boys with posterior urethral valves during childhood and adolescence. MATERIALS AND METHODS: A total of 12 prepubertal boys with posterior urethral valves presenting before age 1 year was followed from ages 4 to 14 years and compared to 6 postpubertal boys with posterior urethral valves. Urodynamic evaluations and renal function studies were performed repeatedly. RESULTS: Patients had a changing urodynamic pattern with instability decreasing with time, increasing bladder capacity and commonly an unsustained voiding contraction causing emptying difficulties. Postpubertal boys had high capacity bladders with low contractility. CONCLUSIONS: We suggest that previously described urodynamic patterns of the valve bladder (unstable, poorly compliant and over distended bladders) are variations of the same basic pattern that changes with time toward decompensation.

Does treatment with clean intermittent catheterization in boys with posterior urethral valves affect bladder and renal function?

PURPOSE: In boys with resected posterior urethral valves (PUV) deterioration of renal function is seen during childhood and adolescence, which may partly be caused by bladder dysfunction. We present data on renal and bladder function initially and at followup of boys with PUV in whom the bladder dysfunction has been treated since infancy. MATERIALS AND METHODS: The study included 35 boys with PUV. Bladder regimen, including early toilet training from the age of 1.5 years and detrusor relaxant drugs for the treatment of incontinence from ages 4 to 6 years, was introduced to all patients. A total of 19 boys were started on clean intermittent catheterization (CIC) at a median age of 8 months due to pronounced bladder dysfunction with poor emptying, unsafe pressure levels, high grade reflux and renal impairment. RESULTS: No serious complications of CIC have been seen during followup. Of the 19 boys 2 stopped performing CIC due to noncompliance of the parents at 1 and 3 years, respectively. Initial renal function, measured as median glomerular filtration rate (GFR) in percent of expected for age, was 60% in the CIC group and 90% in the nonCIC group. At followup at a median age of 8 years the CIC group (n = 14, 3 transplanted boys excluded) had an increase in median differential GFR (difference between followup and initial GFR) of 7% (p <0.01), which was similar increase to that of the nonCIC group. In the 2 boys who stopped performing CIC renal function deteriorated with a median differential GFR of -24%. In the CIC group detrusor instability decreased. Poor compliance was seen in 6 of the 19 boys initially and only one remained poorly compliant. In 1 of the boys who stopped performing catheterization a low compliant bladder developed. In all of the other cases bladder capacity increased more than expected for age. CONCLUSIONS: The results suggest that treatment of bladder dysfunction in boys with PUV can counteract the deterioration in renal function seen during childhood but the number of patients in our study is limited.

Four-hour voiding observation in healthy infants.

PURPOSE: We present the 4-hour voiding observation as a method for basic assessment of bladder function in infants and nontoilet trained children. MATERIALS AND METHODS: Voiding pattern, including number of voidings, voided volume, bladder capacity and residual urine for 4 hours, was determined noninvasively in 43 healthy infants. RESULTS: The infants voided an average of 1 time per hour but with great variability. Bladder capacity increased with age according to the formula, 38 + 2.5 x age (months). Mean residual urine plus or minus standard deviation was 4.6 +/- 3.0 ml. In all infants residual volume was less than 5 ml. at least once during observation. CONCLUSIONS: The 4-hour voiding observation is an easy noninvasive method of characterizing the voiding pattern, focusing especially on emptying difficulties, in infants and nontoilet trained children.

Natural filling cystometry in small boys with posterior urethral valves: unstable valve bladders become stable during sleep.

PURPOSE: Our aim was to demonstrate the voiding pattern in small boys with posterior urethral valves during the day and night. MATERIALS AND METHODS: Long-term natural filling and standard cystometry was performed in 16 boys 1.4 to 6 years old (mean age 3.4) in whom posterior urethral valves were diagnosed in infancy. The boys were divided into 2 groups according to whether they had day incontinence. RESULTS: All boys had instability in the daytime but at night bladders were mainly stable. Voiding frequency during the day was high at a mean of 1.7 and 0.5 voidings per hour in the day incontinent and day continent groups, respectively, compared to 0.1 voiding per hour at night in both groups. Voiding detrusor pressure was higher and functional bladder capacity was lower during the day than at night in both groups. CONCLUSIONS: Natural filling cystometry revealed pronounced instability during the day and stable bladders at night. This difference between day and night is an important factor contributing to frequent small voidings during the day, dry nights and high bladder volume in the morning.

Four-hour voiding observation in young boys with posterior urethral valves.

PURPOSE: We evaluated 4-hour voiding observation as a method of basic assessment of bladder dysfunction in young boys with posterior urethral valves. MATERIALS AND METHODS: Voiding pattern, including number of voids, voided and residual urine volume, and bladder capacity, was determined noninvasively in 24 boys younger than 4 years with posterior urethral valves and compared to that of healthy age matched controls. Results were then compared to those of standard cystometry. RESULTS: The number of voids was higher, voided volume was smaller and residual urine volume was higher in the posterior urethral valve group. There was no difference in voiding pattern before and after removal of the anatomical obstruction. Voided and residual urine volume, and bladder capacity were higher on standard cystometry than on voiding observation. CONCLUSIONS: Four-hour voiding observation is an easy noninvasive method that focuses on emptying difficulties and clearly detects differences in voiding patterns between boys with posterior urethral valves and healthy, nontoilet trained children. We recommend the method as a complement to standard cystometry for the diagnosis and followup of bladder dysfunction in young boys with posterior urethral valves to identify the need for treatment.