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Background: In the last decades, the average age for toilet training has increased in the western world. It is suggested that the postponed initiation of toilet training is a contributing factor to problems related to bowel and bladder control. Functional gastrointestinal and urinary tract disorders are prevalent in childhood, causing suffering in affected children and for their families, and consuming healthcare resources. To evaluate whether assisted infant toilet training can prevent functional gastrointestinal and urinary tract disorders in young children, we are conducting a randomized intervention study with a 4-year follow-up., Methods: This randomized two-armed intervention study will include 268 Swedish infants recruited at six child healthcare centers in Region Dalarna located in the central part of Sweden. The intervention entails parents being instructed and practicing assisted infant toilet training with their child. Children are randomized to start assisted infant toilet training at 0-2 months or at 9-11 months of age. The primary objective is to determine the efficacy of assisted infant toilet training initiated at 0-2 months on the prevalence of functional gastrointestinal disorders (defined as infant colic, infant dyschezia and/or functional constipation) up to the age of 9 months. Secondary objectives are to evaluate whether assisted toilet training initiated during the first year of life reduce the prevalence of functional gastrointestinal disorders (defined as functional constipation, gastrointestinal symptoms and/or stool toileting refusal) and urinary tract disorders (defined as bladder dysfunction and/or urinary tract infections) up to the age of 4 years. Furthermore, infant-to-mother attachment, parental stress, the toilet training process and overall parental experiences will be evaluated/explored., Discussion: This protocol article presents the rationale and design of a randomized two-armed intervention study that will determine the efficacy of assisted infant toilet training on functional gastrointestinal disorders up to the age of 9 months. Furthermore, the study will evaluate whether assisted infant toilet training during the first year of life can prevent functional gastrointestinal and urinary tract disorders in children up to 4 years of age. If effective, assisted infant toilet training could be recommended in child healthcare settings and new evidence-based guidelines on infant toilet training could be implemented., Trial Registration: The study protocol was retrospectively registered at ClinicalTrials. gov  ( NCT04082689 ), initial release June 12th, 2019)., (© 2022. The Author(s).)

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., (Copyright © 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

This review aims to provide researchers and clinicians involved with the adult lower urinary tract with background knowledge regarding the early development of bladder function and its most common disturbances in childhood. Bladder development begins in weeks 4-6 and the detrusor muscle is formed during weeks 9-12 of gestation. Higher CNS centres are involved in micturition at birth, and the infant usually wakes up, at least briefly, to void. Voiding during the first years of life is often incomplete, owing to detrusor-sphincter dyscoordination, but this disappears when bladder control is attained. Approximately 5-10% of 7-year-old children suffer from daytime incontinence and/or nocturnal enuresis, and a few per cent of them will not outgrow it. Daytime incontinence in childhood is usually attributable to detrusor overactivity, although it is unclear to what extent it is the detrusor or the micturition reflex per se that is overactive. Enuresis - nocturnal incontinence - is caused by either nocturnal polyuria and/or nocturnal detrusor overactivity, in both cases combined with high arousal thresholds. Bladder problems in childhood constitute a risk factor for the development or persistence of bladder problems in adulthood., (© 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.)

Objective: To describe longitudinally the development of micturition patterns in children who are potty trained early., Subjects and Methods: Healthy children in Vietnam from newborn up to 1 year were investigated every 3 months. This included mapping of the micturition pattern through the 4-h micturition observation method., Results: Forty-seven children participated in all five investigations. At the ages of newborn, 3, 6, 9 and 12 months, 70%, 82%, 91%, 99% and 100% of the mothers, respectively, were potty training their children. Mean lowest bladder volume (voided volume + residual urine) triggering a micturition was 18 ml at the age of 2 weeks compared to 33 ml at 12 months. Post-void residual urine decreased according to age, and already at 9 months was less than 7 ml (mean 0.7 ml)., Conclusions: The dyscoordination between the sphincter and detrusor muscle seems to have already disappeared at the age of 9 months in infants who are potty trained very early. These findings suggest that potty training can be beneficial in small children with urinary tract infections or renal scars., (Copyright © 2009 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Purpose: Reports concerning bladder dysfunction patterns in infants with high grade vesicoureteral reflux during the first year of life vs older children with reflux are contradictory. To describe the development of bladder function characteristics in children with congenital dilating reflux, we evaluated such infants urodynamically and followed them regularly for a 3-year period., Materials and Methods: A total of 89 males and 25 females with grade III to V dilating reflux were evaluated 3 times using videocystometry at mean ages of 6, 20 and 40 months., Results: Characteristics of the urodynamic pattern at 6 months could not be differentiated from normal patterns for that age, including low and normal bladder capacity, high voiding pressure levels, dyscoordination at voiding (80%) and overactivity during filling (60%). However, at 20 months the overall pattern was different, including increased bladder capacity and residual volume, normal voiding pressure, persistent overactivity during filling and dyscoordination at voiding. Bladder dysfunction was seen in 48 children (42%) at 20 months, of whom 34 primarily had high bladder capacity with incomplete emptying (dilated bladder dysfunction) and 14 had overactive bladder. Predictors for development of dilated bladder dysfunction at followup were high residual urine at 6-month examination and recurrent urinary tract infections. Recurrent infections were significantly correlated to high residual urine at all investigations and to detrusor overactivity at the 20-month examination., Conclusions: Urodynamic patterns changed between the first and second year of life in patients with dilating reflux, from an immature pattern with high pressure levels to high capacity bladder with incomplete voiding. Therefore, bladder dysfunction, which was seen in 42% of patients, was only possible to diagnose after the first year of life and was mainly seen as high capacity bladder with incomplete voiding.

Purpose: To investigate whether mode of occurrence of vesicoureteral reflux (VUR), during micturition (M), during filling without increase in pressure (passive, P) or in response to an overactive contraction (OA), can be explained by differences in bladder function. Also, to study if the mode of occurrence of VUR can predict spontaneous resolution., Materials and Methods: There were 93 infants (68 boys and 25 girls) with VUR (grade III-V) included. Videocystometry was performed at median ages 5, 22 and 32 months registering grade and mode of reflux and bladder function characteristics., Results: Mode of occurrence of reflux changed with age. During infancy P, OA and M reflux comprised almost equal parts. At follow up, P reflux had increased and both OA and M reflux had decreased. This was partly due to a significantly higher probability of spontaneous resolution for M than P reflux, at 40 months (42 vs 18%). P and M reflux were significantly correlated to bladder function characteristics. P reflux was seen in children with high bladder capacity and occurred early in filling. Other predictors were higher age within the respective group and female sex. M reflux was correlated to lack of residual urine, low bladder capacity and absence of overactivity. Other indicators were male sex and low-grade reflux., Conclusions: P and M reflux correlate to different bladder patterns: P with high bladder capacity and M with low bladder capacity and without signs of bladder dysfunction. M seems to be benign with a higher resolution rate.

Purpose: We determine by ultrasonography the range of dT in carefully treated and followed children with myelomeningocele, and evaluate the role of such measurements for the understanding of bladder abnormalities in these patients., Materials and Methods: We studied 66 children and young adults with MMC (34 males and 32 females, median age 8.1 years, range 1.1 to 20.1). Detrusor thickness was measured with a previously established ultrasonographic technique and the results were compared to those in normal children. The variation in detrusor thickness with degree of bladder dysfunction as well as with bladder wall trabeculation, kidney function and anticholinergic treatment was studied., Results: The detrusor of the ventral wall was slightly thinner in children with MMC compared to normal. No significant variation in dT was found for different degrees of bladder dysfunction, bladder wall trabeculation, kidney function or anticholinergic treatment. Boys had thicker detrusor of the ventral wall than girls., Conclusions: Children with MMC, followed closely and treated according to international standards, do not acquire detrusor thickening as measured by ultrasonography. The detrusor thickness did not correlate with the degree of bladder dysfunction or renal function, or with anticholinergic treatment. Bladder wall trabeculation at VCU was not associated with bladder wall thickening on ultrasonography. We postulate that in a closely monitored and actively treated population of patients with MMC muscular hypertrophy and the development of connective tissue in the bladder wall is kept to a minimum.

Purpose: The short-term prognosis for boys with posterior urethral valves (PUV) has improved in recent decades, but the long-term prognosis in terms of renal and bladder function and fertility is still a matter of great concern. This study is a followup of boys with PUV and dilated upper urinary tract treated in 1956 to 1970 at the Children's Hospital in Göteborg, Sweden., Materials and Methods: The records of 54 boys treated for PUV were reviewed. Of 27 boys with PUV and upper urinary tract dilation, 5 boys (18%) died at an early age and 3 boys were lost to followup during adolescence, leaving 19 to be included in the followup. They all answered a questionnaire about renal and bladder function and paternity., Results: Of the 19 men 32% were uremic, 21% had moderate renal failure and 47% had not been checked since adolescence. There were signs of bladder dysfunction in 40% and all these subjects had bladder symptoms suggesting detrusor weakness as the cause. All the men were continent. The ability to father children was dependent on whether or not the man was uremic., Conclusions: This long-term followup study emphasizes the importance of checking renal and bladder function throughout life in men born with PUV. Increasing attention to bladder dysfunction and its early treatment could probably improve the long-term prognosis.

Purpose: We describe the voiding pattern and acquisition of bladder control in healthy children up to age 6 years., Materials and Methods: We determined age for daytime and nighttime dryness, voiding patterns, voiding volumes and post-void residual volume per 4 hours individually and noninvasively every 3 months up to age 3 years and every 6 months up to age 6 years in 36 female and 23 male patients using 4-hour voiding observation and uroflowmetry/ultrasound., Results: Median age for attaining daytime and nighttime dryness was 3.5 and 4 years, respectively. No significant difference was found between girls and boys. All but 1 child attained daytime dryness an average of 10 months before attaining nighttime dryness. Bladder sensation was reported in 31%, 79% and 100% of patients at ages 2, 3 and 4 years, respectively. Median bladder capacity was 67 ml, 123 ml and 140 ml at years 1, 3 and 6, respectively. Median post-void residual volume was 5.5 ml, 0 ml and 2 ml at ages 1, 3 and 6 years, respectively., Conclusions: Today bladder control is acquired at a later stage despite earlier awareness of bladder function. The occurrence of bladder sensation from age 1.5 years motivates an earlier start with toilet training. Infants with small post-void residual volume at age 6 months or large bladder capacity will probably attain daytime dryness earlier than those with large post-void residual volume at age 6 months or small bladder capacity.

The purpose with the present review was to describe what could be considered as normal urodynamic findings in neonates and infants. During the first months of life, urodynamics were characterised by small bladder capacity and high voiding pressure levels, the latter especially marked in male infants. Also dyscoordination at voiding was a common finding. However, detrusor overactivity (unstable contractions) during filling was uncommon in infants. Towards the end of infancy, findings became more in accordance with what is seen in older children. Concluding these findings concerning urodynamic pattern in early infancy high voiding pressure levels must be looked upon as normal and the same is true for intermittent increase in activity in the pelvic floor during voiding. However, instability during filling is rarely seen.

The purpose with the present review was to characterise bladder function in healthy preterm and full-term infants from findings in studies using the four-hour voiding observation. Characteristics of the free voiding pattern were very similar in preterm and full-term infants. The frequency of voidings was once an hour, bladder volume inducing voiding varied, infants often woke up before voiding and the bladder was not completely emptied at every voiding. Furthermore, interrupted voidings interpreted as a detrusor-sphincter dyscoordination, were seen and were clearly an immature phenomenon since the frequency was high in the preterm infants and then decreased. Concluding these findings the voiding pattern seems to be immature early in life and there is distinct evidence for a connection to the CNS already in the preterm infant.

Purpose: Bladder function in healthy neonates and its development during infancy are described., Materials and Methods: Results of free voiding studies of healthy neonates and infants using 4-hour voiding observation and urodynamics studies were reviewed., Results: According to these studies, voiding in the healthy neonate is characterized by small, frequent voids of varying volume in the individual case and interrupted voiding in 30% of the cases. Interrupted voiding is clearly an immature phenomenon since it is seen in 60% of preterm neonates and disappears completely before the age of toilet training. These voidings are considered to be due to a dyscoordination between the sphincter and detrusor, which has also been observed on urodynamic studies and which probably also explains incomplete emptying seen in this age group. Emptying remains incomplete to the age of toilet training when residual urine is median 0 ml. during 4 hours of observation. Voiding rarely occurs during quiet sleep even in the neonatal period, when signs of arousal are often noted before voiding. However, voiding during sleep in 60% occurs of preterm infants, indicating that it may be due to maturation of the central nervous system. Bladder instability is rarely seen in healthy neonates and infants according to urodynamic studies but hyperactivity is suggested in the neonatal bladder with premature voiding contractions after only a few milliliters of filling and with leakage of urine. This latter phenomenon probably explains the low cystometric bladder capacity in this age group. High voiding pressure levels also accompany this low bladder capacity., Conclusions: Thus, it can be suggested that the neonatal bladder is regulated by neuronal pathways with connections to the cerebral cortex in the neonatal period, which is contrary to the earlier concept of voiding as an automatic event in response to a constant volume in the bladder. This theory does not mean that voiding is conscious or voluntary in this age group, but only that the voiding reflex disturbs the neonate. New characteristics include the concept of physiological dyscoordination, such as hyperactivity of the detrusor seen as low bladder capacity, and high voiding pressures in the neonatal period.

Purpose: We evaluate voiding cystourethrography as a method for identifying bladder instability in infants., Materials and Methods: Cystometry was combined with voiding cystourethrography in 79 male and 64 female infants with first time urinary tract infection. Bladder wall irregularity, elongation of bladder shape, and filling of the posterior urethra were transient radiological signs occurring during bladder filling and were considered to reflect bladder instability. A pediatric radiologist looked for these signs on all 480 films exposed during bladder filling. The results were correlated to simultaneous detrusor pressure recordings. The analysis was repeated independently by a urologist to evaluate the reliability of the radiological signs used., Results: The sensitivity and specificity were both 90% in the evaluation of radiological signs of bladder instability. Filling of the posterior urethra was the least frequently reported radiological sign, which was seen at 53% of unstable contractions. However, when this sign was reported, instability was usually correctly detected (85%). Evaluation accuracy had improved with increasing numbers of noted signs per film. This accuracy had included 29%, 67% and 91% of unstable contractions that were correctly diagnosed when 1, 2 or 3 signs were noted, respectively. The number of noted signs was positively related to the strength of the unstable detrusor contraction. Urologist evaluations had similar results to the radiologist, although the sensitivity was somewhat lower (79% and 90%, respectively)., Conclusions: Unstable detrusor contractions could be identified in infants by evaluation of radiological signs on voiding cystourethrography. Findings of bladder wall irregularity, elongation of bladder shape and filling of the posterior urethra indicated unstable detrusor contraction. The more such findings are observed, the stronger the indication.

The time when we start potty training has become increasingly postponed. This paper discusses the possible negative consequences of this social situation. Depending on the child's maturity, bladder control could be defined as anything from "continence with support of an adult before the age of one year" to "independent social control, unobtainable in our culture before the child is 4 years of age". In toddlers suffering from bladder dysfunction, the impact of potty training improves bladder emptying, decreasing residual urine and resultant urinary tract infection. In toddlers with anatomical and functional anomalies of the urinary tract, early potty training is recommended.

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.

An antenatal ultrasonographic examination of a male fetus at 31, 33 and 36 weeks' gestation revealed grossly abnormal bladder function. The bladder cycle length, residual volumes and the degree of distention all markedly deviated from normal, although hydronephrosis which is indicative of vesico-ureteral reflux could not be detected. Furthermore, postnatally no anatomical urethral obstruction was found to explain the high bladder volumes. Postnatal investigation revealed bilateral reflux and bladder dysfunction with detrusor instability, a reduced bladder capacity and a high voiding pressure similar to that observed in boys with anatomic obstruction of the urethra and/or posterior urethral valves. These findings add to the controversy concerning the genesis of vesico-ureteral reflux and have implications for the prenatal assessment of bladder function in cases of suspected vesico-ureteral reflux.

Purpose: We performed followup investigations of the urodynamic patterns of 11 boys with gross bilateral reflux, which are sometimes characterized by low bladder capacity and hypercontractility of the detrusor., Materials and Methods: Urodynamic evaluations were done a mean of 2 years after the initial assessment during infancy., Results: Initial hypercontractility resolved and bladder capacity increased from below normal to high in the majority of cases. The number of children with instability did not change significantly., Conclusions: The urodynamic pattern at followup was similar to that previously reported as the most common dysfunction in older children with reflux.

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.

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.

In this study the prevalence of bladder dysfunction in 18 children with gross bilateral reflux was investigated via cystometric recordings. In all except 1 infant maximal voiding detrusor pressure was 100 cm. or greater water (range 86 to 244). Pronounced instability during filling (overt instability) with pressure waves above baseline (mean 65 cm. water, range 42 to 194) was found in 9 infants. Another 5 children had evidence to suggest an uninhibited bladder, not manifested as unstable contractions during filling but as covert instability, meaning that the first unstable contraction was transformed into a premature and forceful voiding contraction. The high detrusor pressures found in 18 children with gross bilateral reflux during the voiding phase but also during the filling phase in half of the children suggest that a hypercontractile detrusor may be a contributory factor for the development of reflux even in this age group.

Bladder motility recordings were performed in anaesthetized rats and the effect of the peripherally active opiate agonist loperamide on urinary bladder function was studied. Regional intra-arterial administration of loperamide (0.01-2 mg kg-1) induced weak bladder contraction per se. Loperamide caused an effective dose-dependent inhibition of bladder motility induced by regional injection of the receptor agonists acetylcholine (ACh) and substance P (SP), as well as by peripheral motor nerve stimulation (PNS). Pretreatment with naloxone (0.5 mg kg-1) partially antagonized the inhibitory action of loperamide on the nerve-mediated detrusor contraction. However, the depression of the motor responses induced by the receptor agonists ACh and SP was not influenced. It is suggested that the demonstrated inhibitory effect of loperamide on bladder motility is partially mediated by peripheral opioid receptors. The main non-opioid part of the inhibition might be a direct smooth muscle action.

Unlabelled: Muscle strips from rat and human detrusor were studied using indirect immunofluorescence and electrical nerve stimulation in an organ bath. Immunoreactivity towards dynorphin was observed in varicose nerve fibres in the detrusor muscle and around immunonegative nerve cell bodies in the prevesical ganglia of the rat. In vitro, dynorphin A (1-13) (10(-13)-10(-6) M) strongly facilitated detrusor contraction induced by electrical field stimulation (EFS). This facilitation was counteracted by morphine (10(-10) and 10(-8) M) and naloxone (10(-10) and 10(-8) M) in a competitive manner. The facilitation could also be counteracted by the addition of the kappa-receptor antagonist M(r) 2266 (10(-7) M). Muscarinic blockade, achieved with atropine (10(-6) M), did not alter the effect of dynorphin A (1-13). Addition of phentolamine mesylate (10(-6) M), and propranolol (10(-6) M) per se facilitated the EFS-induced contractions. Both adrenergic blockade as well as the addition of the substance P blocker spantide, counteracted the facilitating effect of dynorphin A (1-13)., In Conclusion: Dynorphin A immunoreactive material was found to be present in nerves in the rat detrusor and in prevesical ganglia. Dynorphin A (1-13) facilitated the detrusor contraction, possibly via actions on kappa-opioid receptors and interaction with non-cholinergic nerves.

Motility recordings in muscle strips from rat urinary bladder were performed and the effect of the opiate agonist loperamide on motor activity was studied. Loperamide induced a concentration-dependent (10(-7)-10(-3) M) inhibition of the contractile response of the detrusor strip of the same order of magnitude after activation of intramural nerves, stimulation of cholinergic receptors with acetylcholine and after direct depolarisation of the cell with potassium. Pretreatment with the opiate-antagonist naloxone (10(-5) M) did not antagonise the inhibitory action of loperamide on bladder motility regardless of the type of activation. Naloxone per se, however, facilitated the nerve-mediated motor response. The inhibitory action of loperamide on the potassium-induced contraction could partly be counteracted by elevation of the calcium concentration in the medium. It is suggested that the demonstrated inhibitory effect of loperamide on bladder motility is a calcium-dependent direct smooth muscle action, without any significant opiate-receptor-mediated action in the present in vitro preparation.

Intravesical pressure recordings of the urinary bladder in anesthetized rats were performed and the role of substance P (SP) in the motor control of this organ was evaluated. Regional injection of SP (0.4 nmoles i.a.) into the superior vesical artery elicited a prompt bladder contraction; this motor response was dosedependent. The detrusor contraction could be completely inhibited by a SP-analogue, (D-Pro2, D-Trp7,9)-SP (45-90 nmoles i.a.). Furthermore, the detrusor contraction evoked by preganglionic stimulation of the pelvic nerves was partially inhibited by the same antagonist in a higher dose (65% reduction at a total dose of 150-300 nmoles). The contractile response to SP (0.5 nmoles i.a.) was also significantly reduced after blockade of muscarinic receptors with atropine (50% reduction at 1 mg/kg i.a.) or after ganglionic blockade with hexamethonium (75% reduction at 25 mg/kg i.v. + 50 mg/kg hr i.a.). Immunocytochemical studies demonstrated the occurrence of SP-immunopositive nerve terminals in the detrusor part of the rat urinary bladder. Based on these findings it is suggested that SP may act as a neurotransmitter/modulator in this organ. The mechanism of action for SP on the detrusor seems to be complex and may involve ganglionic transmission via both types of cholinoceptors as well as direct activation of smooth muscle.

Cystometric recordings were performed in pentobarbitone anaesthetized rats and the effects of baclofen on urinary bladder function were evaluated as their influence on bladder hyperactivity induced by 1-dihydroxyphenylalanine (L-dopa) after peripheral decarboxylase inhibition. The bladder response was inhibited by intracerebroventricularly (i.c.v., 4th ventricle, 0.1 microgram) as well as by systemically administered (10 mg/kg i.v.) baclofen. Intravenous naloxone but not i.v. bicuculline i.c.v. substance P or i.c.v. glutamate antagonized the inhibitory actions of i.c.v. or/and i.v. baclofen. It is suggested that baclofen depresses the hyperactive bladder by a central action that is unrelated to bicuculline sensitive gamma aminobutyric acid mechanisms, substance P or glutamate neurotransmission but that is possibly related to interference with opioid mechanisms.

Central neurotransmitter systems have been activated in anaesthetized rats, while the effects on the urinary bladder have been recorded by cystometric procedures. Stimulation of central catecholamine neurons with the amine precursor L-3,4-dihydroxyphenylalanine (L-DOPA), after peripheral inhibition of the degradating enzyme dopadecarboxylase, resulted in a hyperactive urinary bladder response. This bladder action seems to be elicited mainly via central dopamine receptors, and mediated via neurons of non-catecholamine type. Activation of central muscarinic receptors with oxotremorine, after pretreatment with methylscopolamine, induced a hyperactive urinary bladder response, which is suggested to originate in pontine-mesencephalic structures as well. There might in some instances be an interaction with muscarinic receptors in the generation of the bladder hyperreactivity to L-DOPA, at the pontine-mesencephalic brain level. The bladder response to stimulation of central muscarinic receptors, on the other hand, seems to be independent of intact adrenergic neurons. The peripheral mediation of the bladder response to L-DOPA is propagated via the pelvic nerves; in the peripheral ganglia via cholinergic receptors, but in the bladder detrusor via non-cholinergic as well as non-adrenergic receptors. Activation of central GABA mechanisms with GABA, muscimol and diazepam strongly inhibited the bladder hyperactivity to L-DOPA. This inhibition probably occurred in the pontine-mesencephalic brain area. The results suggest that excitatory dopaminergic and muscarinic receptors, as well as inhibitory gabaergic receptors in the pontine-mesencephalic brain region, are involved in the modulation of the urinary bladder function.

Intravesical pressure recordings were performed in anaesthetized rats, and the effect of morphine on urinary bladder function was studied. The action of morphine was registered as its influence on bladder hyperactivity induced by central catecholaminergic stimulation with 1-dihydroxyphenylalanine (L-DOPA) after peripheral decarboxylase inhibition, and as its action on the response to regional injection of receptor agonists (acetylcholine (ACh), substance P (SP)) and peripheral motor nerve stimulation (PNS). The bladder response to L-DOPA was inhibited by intracerebroventricularly (i.c.v., fourth ventricle, 10 micrograms), as well as by systemically administered (1-5 mg kg-1 i.p.), morphine. Intravenous and i.c.v. naloxone antagonised the inhibitory actions of i.v. and i.c.v. morphine, respectively. Regional intra-arterial administration of morphine (0.01-5 mg) induced a weak bladder contraction per se, with a subsequent slight depression of bladder reactivity to ACh, SP and PNS. It is suggested that the inhibitory effect of morphine on bladder motility in the rat, is mainly mediated by central opioid-receptors. The direct peripheral effects on the detrusor muscle are weak, with an initial contraction followed by slight depression of the reactivity.

Cystometric recordings were performed in pentobarbitone anaesthetized rats and the effects of gammaaminobutyric acid (GABA) mechanisms on urinary bladder function were evaluated as their influence on a bladder hyperactivity induced by 1-dihydroxyphenylalanine (L-DOPA) after peripheral decarboxylase inhibition. The bladder response was inhibited by intracerebroventricular (i.c.v., 4th ventricle) injections of GABA (250 microgram), muscimol (0.2 microgram) and glycine (1,000 microgram) as well as by systemically administered muscimol (4 mg/kg) and diazepam (2 mg/kg). Intravenous (i.v.) bicuculline, but not i.v. strychnine, antagonized the inhibitory actions of intraperitoneal (i.p.) and i.c.v. muscimol and i.v. diazepam while the opposite was true for the inhibitory action of i.c.v. glycine. In rats not pretreated with L-DOPA, i.p. administration of bicuculline (4 mg/kg) after 15 min caused prominent detrusor contractions that were prevented by an infracollicular brain transection. It is suggested that GABA synapses in the pontinemesencephalic brain region may be involved in the modulation of urinary bladder function.

The involvement of central and peripheral cholinergic structures in the mediation of a centrally induced hyperactive urinary bladder response to L-2,3-dihydroxyphenylalanine (L-DOPA), after peripheral decarboxylase inhibition, registered by a cystometric procedure, has been analysed pharmacologically in anaesthetised rats. The urinary bladder response to L-DOPA was unchanged after blockade of cholinergic receptors with methylscopolamine, diminished after atropine and totally inhibited after hexamethonium. In addition, activation of muscarinic receptors in the pontine-mesencephalic brain region with oxotremorine after methylscopolamine pretreatment generates a hyperactive urinary bladder response, mediation of which seems to be independent of endogenous catecholamine stores. It is suggested that cholinergic receptors in the pontine-mesencephalic brain region are of importance for regulation of urinary bladder function in the rat. Furthermore, the bladder hyperactivity induced by L-DOPA might be propagated via muscarinic receptors in this brain area, and mediated peripherally via cholinergic receptors in the autonomic ganglia, but in the bladder detrusor via non-cholinergic receptors.

The aim of the present study was to investigate a possible central monoaminergic influence on the control mechanism of the urinary bladder in rats. A selective central nervous stimulation was accomplished by injection of monoaminergic precursor (L-dopa and 5-HTP) after enzymatic blockade of its peripheral metabolisation. The bladder response was recorded with a cytometric procedure. The central adrenergic stimulation with L-dopa resulted in a hyperactive bladder response, with higher intravesical pressure and more prominent detrusor contractions than in control rats. Injection of 5-HTP had no such effect. The hyperactive bladder response to L-dopa was abolished by prior administration of a central dopamine receptor blocking agent (spiroperiodol). This indicated that the central effect on the bladder was elicited by dopaminergic structures. Peripheral adrenergic stimulation with metabolites of L-dopa--dopamine and noradrenaline--gave no measurable bladder response. The study showed that activation of central adrenergic mechanisms influenced urinary bladder control, i.e. evoked a hyperactive bladder response.

The hyperactive bladder response observed after central adrenergic stimulation with L-dopa, following enzymatic blockade of its peripheral metabolism, was studied in the rat. The bladder response was recorded by a cystometric procedure. The hyperactive bladder action thus produced was noted after transection of the CNS at the level of the superior colliculi but not when the transection was made caudal to the inferior colliculi. No effect was seen after transection of the cauda equina at L6, i.e. parasympathetic decentralisation of the bladder. It is concluded that the hyperactive bladder reaction seen after central adrenergic stimulation is produced in the mesencephalic-pontine region and mediated to the bladder via a central coupling to parasympathetic pathways.

Purpose: We evaluated the rate of complications associated with catheterization and the risk of urethral lesions in girls with myelomeningocele treated with clean intermittent catheterization for a minimum of 10 years. Materials and Methods: We examined the medical records of 31 females with myelomeningocele followed from the start of clean intermittent catheterization until age 11 to 20 years. Catheterization had been performed for a median of 15 years (range 10 to 19). Altogether, catheterization was used for a total of 459 patient-years. Noncoated polyvinyl chloride catheters were used in all cases. Anticholinergic treatment was given during 176 of the patient-years. Results: Complications of catheterization were recorded in 13 patients on 20 occasions. Macroscopic hematuria was seen in 4 individuals. In 2 patients the hematuria was caused by urethral polyps that were cured by resection. Difficulties with catheterization occurred in 12 patients. The problems were solved by temporary use of lubrication or by other minor changes in management. There were no difficulties recorded after puberty. The risk of difficulties at catheterization doubled with the use of a Ch8 to Ch10 catheter compared to a Ch12 or larger catheter, and doubled during assisted clean intermittent catheterization compared to clean intermittent self-catheterization. Conclusions: There were remarkably few problems associated with clean intermittent catheterization in these females with myelomeningocele, despite long treatment periods and use of noncoated polyvinyl chloride catheters. Clean intermittent self-catheterization and large size catheters were associated with few complications. [Copyright &y& Elsevier]