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Aim: To detect effects of desmopressin on sleep in enuretic children and to look for polysomnographical differences between responders and non-responders to desmopressin treatment.Methods: Twenty-one children with primary nocturnal enuresis were examined polysomnographically before treatment. All but one of the children then received treatment with desmopressin in standard dosage, and the response was documented. Seven of the children underwent a second polysomnographic registration while on treatment.Results: The time interval (+/- 1 SD) between sleep onset and the enuretic episode was 92 +/- 67 min without medication and 372 +/- 157 min when desmopressin was given (p = 0.003). Standard polysomnographic variables were not affected by the drug. Ten children were desmopressin responders and 10 were non-responders. The total sleep time was 455 +/- 56 min in the former and 408 +/- 31 min in the latter group (p = 0.04). The responders spent 27.4 +/- 5.5% of their total sleep time in rapid eye movement sleep, compared with 18.2 +/- 6.5% in the non-responder group (p = 0.004).Conclusion: Desmopressin has no major effects on sleep as such but does delay bladder emptying. Enuretic children responding to desmopressin treatment have more rapid eye movement sleep than therapy-resistant children. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Dysphagia is not unusual following repair of esophageal atresia (EA). The lack of a uniform definition has led to a variance when it comes to reporting the prevalence of dysphagia among patients operated on for EA. Our aim is to estimate the occurrence and degree of dysphagia, using a numerical score with its statistical versatility independent of a specific definition. The results are used to find early risk factors of dysphagia within this patient group. The results are also used to see whether we can find a correlation between dysphagia and symptoms of gastroesophageal reflux (GER) and quality of life (QoL). Methods: 79 consecutive survivors operated on for EA in Gothenburg between 1968 and 1983 were located. Hospital charts were reviewed and patients received questionnaires on dysphagia, symptoms of GER and QoL. Dysphagia was measured by a numerical score, symptoms of GER were extracted using a predetermined questionnaire (GerdQ), and QoL was determined using the generic questionnaire SF-36. Results: 73 patients (92.4 % ) returned the questionnaires. In order to make the study group as homogeneous as possible with regard to the malformation we choose to study the 63 patients representing the vast majority: those with Gross type C. 36 patients (57 % ) had symptoms of dysphagia to varying degrees. We did not find any aggravating factors in their hospital charts nor did we find any correlation to the most recent demographics. There was a significant difference in dysphagia scores when we compared Gross type C to the often more complex type A (p < 0.05). We did not find any correlation to heartburn but a strong correlation to regurgitation with an OR of 2.8 (95 % CI: 1.2 - 6.6). The QoL was good for this patient group, and we did not find any correlation between QoL and the dysphagia score. Conclusions: The dysphagia score provides easy-to-use results when it comes to evaluating the potential influence of dysphagia. Dysphagia is common within this patient group. Patients operated on for EA Gross type A seem to do worse when it comes to dysphagia. Regurgitation is associated with dysphagia, which could imply that GER is an aggravating factor. Further studies to support this finding will show whether there is a correlation between the dysphagia score and the results of 24-h pH-monitoring. If so, this could mean that treating GER might decrease dysphagia, at least in this patient group. [ABSTRACT FROM AUTHOR]

Aims: A study was undertaken to examine whether poor self-rated health (SRH) can independently predict all-cause mortality during 22-year follow-up in middle-aged men and women. Subjects and methods: Data are derived from a population-based study in Malmö, Sweden. This included baseline laboratory testing and a self-administered questionnaire. The question on global SRH was answered by 15,590 men (mean age 46.4 years) and 10,089 women (49.4 years). Social background characteristics (occupation, marital status) were based on data from national censuses. Mortality was retrieved from national registers. Results : At screening 4,261 (27.3%) men and 3,085 (30.6%) women reported poor SRH. Among subjects rating their SRH as low, 1,022 (24.0%) men and 228 (7.4%) women died during follow-up. Corresponding figures for subjects rating their SRH as high were 1801 (15.9%) men and 376 (5.4%) women. An analysis of survival in subjects reporting poor SRH revealed an age-adjusted hazard risk ratio (HR, 95%CI) for men HR 1.5 (1.4-1.7), and for women HR 1.4 (1.2-1.6). The corresponding HR after adjusting for possible social confounders was for men HR 1.3 (1.1-1.4), and women HR 1.1 (0.9-1.4). When additional adjustment was made for biological risk factors the association for men was still significant, HR 1.2 (1.1-1.3). Conclusion: Poor SRH predicts increased long-term mortality in healthy, middle-aged subjects. For men the association is independent of both social background and selected biological variables. The adjustment for biological variables can be questioned as they might represent mediating mechanisms in a possible causal chain of events. [ABSTRACT FROM AUTHOR]

Objective To investigate predictive factors for the outcome of treatment of primary monosymptomatic nocturnal enuresis (PMNE) with desmopressin. Patients and methods Data from a large open multicentre study were analysed. The study comprised 399 children with PMNE who were recruited for long-term desmopressin treatment. Before treatment a history was taken and the children observed for 4 weeks. After a 6-week dose-titration period with desmopressin, the children were classified into four groups depending on the response rate. Results The children who improved during desmopressin treatment were older, had fewer wet nights during the observation period and had only one wet episode during the night, mostly after midnight. Many of them did not require the maximum dose of desmopressin to become dry. No hereditary factor for the response to desmopressin was found. Conclusion Those most likely to be permanently dry with desmopressin treatment are older children who respond to 20 µg desmopressin and who do not wet frequently. [ABSTRACT FROM AUTHOR]

Objective To study the long-term efficacy and safety of desmopressin treatment in children with primary monosymptomatic nocturnal enuresis. Patients and methods Children (aged 6–12 years) with nocturnal enuresis were recruited into an open multicentre trial. All children underwent an observation period of 4 weeks before starting a 6-week dose-titration period with desmopressin. If the number of wet nights decreased by more than half during medication, they began long-term treatment on 20–40 μg desmopressin. To test for cure and avoid overtreatment, the medication was interrupted for one week every third month. Results Of the 399 children forming the intention-to-treat cohort, 245 halved their number of wet nights and started long-term treatment. During the periods off medication, 77 children were dry and at the end of the study another 73 (still on medication) reduced the number of wet nights to ≤10% of that during the observation period. A further 51 children halved the number of wet nights compared with the observation period. No serious adverse events occurred. Conclusion Long-term treatment with nasal desmopressin at a main dose of 40 μg is an effective and safe treatment for monosymptomatic nocturnal enuresis. [ABSTRACT FROM AUTHOR]

Central and peripheral administration of DDAVP increase locomotor activity in rats in doses that alter brain dopamine neurochemistry. In order to delineate the role of catecholamines in this behavioural effect of DDAVP, the effects of different catecholamine manipulating agents on DDAVP-induced locomotor stimulation were studied in rats. The catecholamine depleting agent reserpine (5 mg/kg), administered alone or together with the catecholamine synthesis inhibitor α-methyltyrosine (250 mg/kg), completely prevented the locomotor stimulatory effect of DDAVP. The dopamine D1 receptor antagonist Sch-23390 (0.01 and 0.03 mg/kg) significantly antagonized the DDAVP-induced locomotor stimulation when adminis-tered in the higher dose, that also produced a significant reduction of locomotor activity per se, whereas the dopamine D2 receptor antagonist raclopride (0.08 and 0.16 mg/kg) had no significant effect. The two dopamine blockers administered together produced a significant, dose-dependent reduction of DDAVP-induced locomotor stimulation, while controls were not significantly affected. Also the α-adrenoceptor antagonist phenoxybenzamine decreased the DDAVP-induced locomotor stimulation in a dose (20 mg/kg) that did not influence locomotor activity in controls, and, finally, administration of Sch-23390, raclopride and phenoxybenzamine antagonised the DDAVP-induced effect in a dose combination that failed to influence locomotor activity per se. In vivo microdialysis experiments in awake, freely moving rats indicated that DDAVP increases dopamine overflow in the nucleus accumbens, a brain area of importance for initiation of locomotor activity, by approximately 25%, as compared to baseline levels. Taken together, these results indicate that the central stimulatory action of DDAVP involves granula-mediated dopamine release and subsequent activation of dopamine D1 and D2 receptors, and that α-adrenoceptors possibly also are involved. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate Kock reservoir function in children and adolescents operated for congenital urinary incontinence and to determine the complication rate. Reservoir function was investigated in 13 children (age range 10.8-16 years) and 7 adolescents (age range 16-18 years) through enterocystometry, enterocystoscopy and patient history. Patients were followed up for 3-10 years. The follow-up was reported as early (3 months-2 years) and late (2-10 years) postoperative periods. At early follow-up reservoir capacity was high in four patients and normal in the remaining patients. A low reservoir pressure was accompanied by high capacity and compliance. On enterocystometry first sensation for emptying was experienced in 82% of patients at early follow-up and 92% at late follow-up. Reservoir contractions were recorded in 60% of patients at early follow-up and 65% at late follow-up. The contractions were recorded at an average reservoir capacity of 270 ml at early follow-up and 340 ml at late follow-up. The complication rate was high in the child group compared with that in adolescents. Of 13 patients with at least one reservoir complication 10 were from the child group. Nipple dysfunction (angled nipple, prolapsed or stenosed stoma) occurred in 35% of patients, stones in 40% and bleeding during catheterization in 15%. Revision was performed in 38% of the child group and 15% of the adolescents. Reservoir perforation was observed in two patients at 6 and 9 years postoperatively. At late follow-up continence was excellent in 17 of 19 patients and good in 2. We conclude that the Kock reservoir is a good modality for urinary diversion, but the complication incidence is high in the child group (<16 years). Stability of the reservoir in terms of volume and low internal pressures was achieved one year after operation, except in the patients with infrequent reservoir emptying. A time-related increase in the reservoir sensitivity and contractility was... [ABSTRACT FROM AUTHOR]

Isometric recordings of mechanical activity in muscle strips from rat and human detrusor were performed and the effect of μ- and δ-opioid receptor stimulation and blockade on detrusor contraction induced by electrical field stimulation was tested. Stimulation of the opioid μ-receptor with morphine (10-13-10-4 M) and DAGO (10-13-10-6 M) had no significant effect on electrical field stimulation except at one concentration of morphine (10-6 M). Naloxone (10-10-10-5 M) caused a significant facilitation of the electrical field stimulation-induced contraction, which was counteracted by morphine (10-8 M) and the δ-agonist DPDPE (10-8 M) in both rat and human detrusor. Addition of atropine (10-6 M) or hexamethonium chloride (10-6 M) or spantide (10-6 M) did not alter the facilitating effect of naloxone in the rat detrusor. Hexamethonium (10-5 M) decreased the facilitating effect of naloxone on electrical field stimulationinduced contractions in the human detrusor, indicating involvement of ganglionic mechanisms. In human detrusor about 15% of the contractile response was found to be atropine-resistant (10-6 M) and one third of this was found to be resistant to tetrodotoxin (1.5 × 10-6 M). The atropine resistant-response in human detrusor was facilitated by naloxone to the same extent as the atropine-sensitive part. Adrenergic blockade per se, achieved with phentolamine mesylate (10-6 M) and propranolol (10-6 M), caused a significant facilitation of the electrical field stimulation-induced contraction in the rat detrusor but did not affect the facilitating effect of naloxone (10-13-10-5 M). Addition of the δ-agonist DPDPE (10-13-10-5 M) did not significantly change the detrusor response to electrical field stimulation in rat detrusor, but the δ-antagonist naltrindole (10-13-10-5 M) caused a significant facilitation at the highest concentration. In human detrusor, DPDPE 10-8 M significantly reduced the response induced by electrical field stimulation. Conclusion: Blockade of the opioid receptors with naloxone facilitates the detrusor contraction elicited by electrical field stimulation. The existence of a tonic, inhibitory action on the detrusor nerve mediated detrusor contraction by opioid μ- and possibly δ-receptors is suggested. [ABSTRACT FROM AUTHOR]

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 (10−7-10−3M) 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 (10−5M) 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. [ABSTRACT FROM AUTHOR]

Objective To study changes in the urodynamic pattern during the first year of life in patients with myelomeningocele (MMC) and to correlate these to deleterious effects on the upper urinary tract. Patients methods Thirty-four infants with MMC were investigated using cystometry, micturating cysto-urethrography and urography at 1, 4 and 10 months of age. Results Detrusor contractility was characterized by an increase in activity, with hyper-reflexia in 45% initially, increasing to 65% at the 4-month investigation. During the same period, the number of infants with areflexia decreased from 25% to 12%. Between 4 and 10 months, there were only minor changes in detrusor contractility. The number of patients with poorly compliant bladders also increased between the first and fourth month. The number of patients with elevated outlet resistance increased only slightly during the first year, from 32% of all infants at the initial investigation to 40% at the 10-month follow-up. Vesico-ureteric reflux was detected in 12 of the patients during the year, with five already diagnosed at the first investigation. Almost all refluxes were cured with clean intermittent catheterization, with additional pharmacological therapy in two patients; one patient required a vesicostomy. Conclusions This study indicates that detrusor activity, and to some extent outlet resistance, change during the first year of life in infants with MMC. The changes were mainly increases in activity and occurred mostly between the first and fourth months of age. There was a strong correlation between the occurrence of reflux and poor compliance, hypercontractility and outlet obstruction. [ABSTRACT FROM AUTHOR]

Thirteen patients, 10 with classical Hirschsprung's disease and 3 with total colonic aganglionosis, were operated upon by anterior resection (11 cases) or pull-through (2 cases) and the anastomosis was constructed with a circular stapler. The age at operation ranged from 9 months to 17 years (median 17 months). A very low resection was obtained, with the level of anastomosis less than 2 cm from the dentate line. The anastomosis was covered by a temporary enterostomy in all but 2 patients. One dorsal anastomotic leak was demonstrated at radiological follow-up. No further anastomotic complications were observed, and all enterostomies were closed within 10 weeks post-resection. The use of a circular stapler is recommended as a modification of the Rehbein operation or the Swenson pull-through. [ABSTRACT FROM AUTHOR]

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) (10-10M) strongly facilitated detrusor contraction induced by electrical field stimulation (EFS). This facilitation was counteracted by morphine (10 and 10M) and naloxone (10 and 10M) in a competitive manner. The facilitation could also be counteracted by the addition of the K-receptor antagonist Mr 2266 (10M). Muscarinic blockade, achieved with atropine (10M), did not alter the effect of dynorphin A (1-13). Addition of phentolamine mesylate (10M), and propranolol (10M) 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 K-opioid receptors and interaction with non-cholinergic nerves. [ABSTRACT FROM AUTHOR]

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-Pro, D-Trp)-SP (45-90 nmoles i.a.). Further-more, 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. [ABSTRACT FROM AUTHOR]

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 methylsopolamine 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. [ABSTRACT FROM AUTHOR]

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 μg) 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. [ABSTRACT FROM AUTHOR]

Cystometric recordings were performed in pentobaribitone 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 μg), muscimol (0.2 μg) and glycine (1,000 μg) 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. [ABSTRACT FROM AUTHOR]