Primary enuresis: relative success of three methods of treatment.

A total of 169 children with primary enuresis were treated by one of three methods--use of a special diet, imipramine, or a waking device (the Mozes detector). Of 64 who received the diet 1 (1.6%) was cured; of 62 who were treated with imipramine 13 (20.9%) were cured; and of 43 who used the detector 23 (53.5%) were cured. Results at follow-up remained substantially unchanged for cure. Improvement rate without cure during treatment was higher for the children treated with imipramine than for those treated with the detector, but at follow-up the reverse was true. Parents of children who received the special diet, because they were unimpressed by the rate of improvement, would not permit their children to continue this form of therapy for longer than 1 or 2 months.     

低频电刺激结合康复训练对脊髓损伤神经源性膀胱患者排尿症状、膀胱功能及生活质量的影响

目的:探讨低频电刺激结合康复训练对脊髓损伤(SCI)诱发神经源性膀胱(NB)患者排尿症状、膀胱功能及生活质量的影响。方法:选取2017年3月～2019年12月期间我院收治的SCI诱发NB患者97例,根据随机数字表法分为对照组(n=48)和研究组(n=49),对照组患者予以康复训练,研究组在对照组基础上联合低频电刺激,比较两组患者排尿症状、膀胱功能、生活质量及并发症发生情况。结果:两组治疗2周后、治疗4周后日膀胱内压力、24 h单次排尿量、排尿次数、膀胱容量均较治疗前增加,且研究组高于对照组(P0.05);残余尿量均较治疗前下降,且研究组低于对照组(P0.05)。两组治疗2周后、治疗4周后膀胱功能积分均较治疗前下降,且研究组低于对照组(P0.05)。两组治疗4周后情感职能、躯体疼痛、精神健康、活力、生理职能、生理机能、健康状况、社会功能维度评分均升高,且研究组高于对照组(P0.05)。研究组并发症总发生率低于对照组(P0.05)。结论:低频电刺激结合康复训练治疗SCI诱发NB患者,可有效改善患者排尿症状,提高其膀胱功能及生活质量,同时还可减少并发症发生率,具有一定的临床应用价值。     

COX-2 and prostanoid expression in micturition pathways after cyclophosphamide-induced cystitis in the rat

The purpose of this study was to determine the role of cyclooxygenase-2 (COX-2) and its metabolites in lower urinary tract function after induction of acute (4 h), intermediate (48 h), or chronic (10 day) cyclophosphamide (CYP)-induced cystitis. Bladders were harvested from euthanized female rats for analyses. Conscious cystometry was used to assess the effects of a COX-2-specific inhibitor, 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl2(5H)-furanone (DFU, 5 mg/kg sc), a disubstituted furanone, in CYP-induced cystitis. COX-2 mRNA was increased in inflamed bladders after acute (12-fold) and chronic (9-fold) treatment. COX-2 protein expression in inflamed bladders paralleled COX-2 mRNA expression. Prostaglandin D2-methoxime expression in the bladder was significantly (P < or = 0.01) increased in acute (3-fold) and chronic (5.5-fold) cystitis. Prostaglandin E2 was significantly (P < or = 0.01) increased (2-fold) in the bladder with intermediate (1.7-fold) and chronic (2.6-fold) cystitis. COX-2-immunoreactive cell profiles were distributed throughout the inflamed bladder and coexpressed histamine immunoreactivity. Conscious cystometry in rats treated with CYP + DFU showed increased micturition intervals 4 and 48 h after CYP treatment and decreased intravesical pressures during filling and micturition compared with rats treated with CYP + vehicle. These studies suggest an involvement of urinary bladder COX-2 and its metabolites in altered micturition reflexes with CYP-induced cystitis.     

Functional and morphological modifications of the urinary bladder in aging female rats

In female Wistar/Rij rats, 10 and 30 mo old, the micturition profiles in conscious animals, the contractile responses of the isolated urinary bladder, and the histology of the vesical tissue have been investigated. During cystomanometry, 60% of conscious senescent rats, but only 25% of young adult rats, showed spontaneous contractions during the bladder-filling phase. In aging rats, micturition pressure and duration of micturition were significantly higher by approximately 40-50%. In contrast, bladder capacity, bladder compliance, micturition volume, and residual volume were not modified with age. In vitro, the contractile responses of the bladder body to KCl, carbachol, arecoline, and alpha,beta-MeATP were similar in tissues from young adult and senescent rats. In contrast, maximum responses to noradrenaline, but not phenylephrine, were two times greater in the older rats. Isoprenaline exhibited the same potency in relaxing KCl-precontracted bladder body of 10- and 30-mo-old animals. Morphometric analysis showed a significant increase in the mean thickness of the muscularis layer with age, whereas the collagen density significantly decreased in the muscularis and in the lamina propria layers. The fact that the majority of senescent rats displayed bladder instability and increased response to alpha-adrenergic agonists suggests that this strain of rat seems a good model for the aged human. However, other characteristics of the aging human urinary tract (urinary frequency, decreased cystometric capacity, and decreased detrusor contractility associated with fibrosis) are not present.     

Activation and inhibition of the micturition reflex by penile afferents in the cat

Coordination of the urinary bladder and the external urethral sphincter is controlled by descending projections from the pons and is also subject to modulation by segmental afferents. We quantified the effects on the micturition reflex of sensory inputs from genital afferents traveling in the penile component of the somatic pudendal nerve by electrical stimulation of the dorsal nerve of the penis (DNP) in alpha-chloralose anesthetized male cats. Depending on the frequency of stimulation (range, 1-40 Hz), activation of penile afferents either inhibited contractions of the bladder and promoted urine storage or activated the bladder and produced micturition. Stimulation of the DNP at 5-10 Hz inhibited distension-evoked contractions and increased the maximum bladder capacity before incontinence. Conversely, stimulation at 33 and 40 Hz augmented distension-evoked contractions. When the bladder was filled above a threshold volume (70% of the volume necessary for distension-evoked contractions), stimulation at 20-40 Hz activated de novo the micturition reflex and elicited detrusor contractions that increased voiding efficiency compared with distension-evoked voiding. Electrical stimulation of the DNP with a cuff electrode or percutaneous wire electrode produced similar results. The ability to evoke detrusor contractions by activation of the DNP was preserved following acute spinal cord transection. These results demonstrate a clear role of genital afferents in modulating the micturition reflex and suggest the DNP as a potential target for functional restoration of bladder control using electrical stimulation.     

Pharmacologic characteristics of bladder micturition function in anesthetized mice

In the present study, we observed the effects of an α(1)-adrenoceptor agonist (phenylephrine), β-adrenoceptor agonist (isoprenaline), muscarinic cholinoceptor agonist (carbachol), and α(1)-adrenoceptor antagonist (doxazosin) on the bladder micturition function in anesthetized mice. Changes in bladder pressure in response to filling and blood pressure were recorded by using a data acquisition system. Phenylephrine (50 to 800 μg/kg) increased vesical micturition pressure in a dose-dependent manner but increased micturition basal pressure only at 800 μg/kg. Carbachol (3 to 7 μg/kg) increased the intercontraction interval and micturition time in a dose-dependent manner but increased micturition basal pressure only at 7 μg/kg. Isoprenaline (10 to 1000 μg/kg) increased micturition time and decreased vesical micturition pressure in a dose-dependent manner. Doxazosin (10 to 1000 μg/kg) did not affect bladder micturition function but dose-dependently inhibited phenylephrine-induced increases in vesical micturition pressure. Carbachol (7 μg/kg) and isoprenaline (1 mg/kg) caused a transient fall in blood pressure, whereas doxazosin (1 mg/kg) had a long-lasting hypotensive effect. The maximal decrease in systolic and mean blood pressure by carbachol did not differ from that by doxazosin and isoprenaline, respectively. Phenylephrine (800 μg/kg) transiently increased the blood pressure of anesthetized mice. These results indicate that activation of muscarinic cholinoceptors decreases voiding frequency and increases bladder capacity in anesthetized mice. Activation of α(1)-adrenoceptors mainly increases vesical micturition pressure, whereas activation of β-adrenoceptors decreases vesical micturition pressure and prolongs micturition time in anesthetized mice.     

Impact of state of arousal and stress neuropeptides on urodynamic function in freely moving rats

Corticotropin-releasing factor (CRF) is a neurotransmitter in Barrington's nucleus neurons. These neurons can coregulate parasympathetic tone to the bladder (to modulate micturition) and brain noradrenergic activity (to affect arousal). To identify the role of CRF in the regulation of micturition, the effects of CRF agonists and antagonists on urodynamics in the unanesthetized rat were characterized. Rats were implanted with bladder and intrathecal or intraperitoneal catheters under isoflurane anesthesia. Cystometry was performed in the unanesthetized, unrestrained state at least 24 h later. In some cases, cortical electroencephalographic activity (EEG) was recorded simultaneously to assess arousal state. During cystometry, the state of arousal often shifted between waking and sleeping and urodynamic function changed depending on the state. Micturition threshold, bladder capacity, and micturition volume were all increased during sleep. The CRF1/CRF2 receptor agonists CRF and urocortin 2 increased bladder capacity and micturition volume in awake but not in sleeping rats. Conversely, the CRF1 receptor antagonists antalarmin and NBI-30775 increased urinary frequency and decreased bladder capacity in awake rats. The present results demonstrate a profound effect of the state of arousal on urodynamic function and suggest that simultaneous monitoring of EEG and cystometry may provide a useful model for studying nocturnal enuresis and other urinary disorders. In addition, the results provide evidence for an inhibitory influence of CRF in the spinal pathway on micturition. Targeting the CRF system in the spinal cord may provide a novel approach for treating urinary disorders.     

Effects of long-chain fatty alcohol on peripheral nerve conduction and bladder function in diabetic rats

Diabetic cystopathy as manifested by an enlarged bladder is mainly caused by peripheral neuropathy. Long-chain fatty alcohol, which has been isolated from the Far-Eastern traditional medicinal plant, Hygrophilia erecta, Hochr., has been found to possess some neurotrophic activities on the central neuron. Cyclohexenonic long-chain fatty alcohol (FA) used in this study were synthesized in order to improve the efficiency of the molecules. The effects of this compound on peripheral nerves, however, have not yet been studied. To get more information, we evaluated the effects of this compound on peripheral nerves in streptozotocin-induced diabetic rats in terms of nerve conduction velocity and bladder function. Three experiments were performed 8 weeks after the administration of streptozotocin to 8-week-old rats: (i) motor sciatic nerve conduction (MNCV), (ii) monitoring micturition behavior in the metabolic cage, and (iii) cystometrogram under urethane anesthesia (CMG). Half of the diabetic rats were treated with FA (8 mg/kg/day, i.p.). The difference in MNCV between control rats (49.0 +/- 2.2 m/s) and untreated diabetic rats (42.4 +/- 0.5 m/s) after 8 weeks reached significance (p = 0.0183). FA-administrated diabetic rats showed an improved MNCV (45.8 +/- 1.2 m/s). We also identified a significant improvement of bladder function in these animals. The diabetic rats had a much higher maximal micturition volume per 24 hours (4.9 +/- 0.4 ml) than control animals (1.5 +/- 0.1 ml). However, the diabetic rats treated with FA had a maximal micturition volume of only 3.7 +/- 0.3 ml. Likewise, the diabetic rats had a CMG bladder capacity of 0.90 +/- 0.14 ml while the diabetic rats treated with FA had a capacity of 0.54 +/- 0.07 ml. These results indicate that cyclohexenonic long-chain fatty alcohol has a beneficial effect on peripheral neuropathy and cystopathy in streptozotocin-induced diabetic rats.     

Pathophysiology of overactive bladder and urge urinary incontinence

Storage symptoms such as urgency, frequency, and nocturia, with or without urge incontinence, are characterized as overactive bladder (OAB). OAB can lead to urge incontinence. Disturbances in nerves, smooth muscle, and urothelium can cause this condition. In some respects the division between peripheral and central causes of OAB is artificial, but it remains a useful paradigm for appreciating the interactions between different tissues. Models have been developed to mimic the OAB associated with bladder instability, lower urinary tract obstruction, neuropathic disorders, diabetes, and interstitial cystitis. These models share the common features of increased connectivity and excitability of both detrusor smooth muscle and nerves. Increased excitability and connectivity of nerves involved in micturition rely on growth factors that orchestrate neural plasticity. Neurotransmitters, prostaglandins, and growth factors, such as nerve growth factor, provide mechanisms for bidirectional communication between muscle or urothelium and nerve, leading to OAB with or without urge incontinence.     

Gentle Mechanical Skin Stimulation Inhibits Micturition Contractions via the Spinal Opioidergic System and by Decreasing Both Ascending and Descending Transmissions of the Micturition Reflex in the Spinal Cord

Recently, we found that gentle mechanical skin stimulation inhibits the micturition reflex in anesthetized rats. However, the central mechanisms underlying this inhibition have not been determined. This study aimed to clarify the central neural mechanisms underlying this inhibitory effect. In urethane-anesthetized rats, cutaneous stimuli were applied for 1 min to the skin of the perineum using an elastic polymer roller with a smooth, soft surface. Inhibition of rhythmic micturition contractions by perineal stimulation was abolished by naloxone, an antagonist of opioidergic receptors, administered into the intrathecal space of the lumbosacral spinal cord at doses of 2–20 μg but was not affected by the same doses of naloxone administered into the subarachnoid space of the cisterna magna. Next, we examined whether perineal rolling stimulation inhibited the descending and ascending limbs of the micturition reflex. Perineal rolling stimulation inhibited bladder contractions induced by electrical stimulation of the pontine micturition center (PMC) or the descending tract of the micturition reflex pathway. It also inhibited the bladder distension-induced increase in the blood flow of the dorsal cord at L5–S1, reflecting the neural activity of this area, as well as pelvic afferent-evoked field potentials in the dorsal commissure at the lumbosacral level; these areas contain long ascending neurons to the PMC. Neuronal activities in this center were also inhibited by the rolling stimulation. These results suggest that the perineal rolling stimulation activates the spinal opioidergic system and inhibits both ascending and descending transmissions of the micturition reflex pathway in the spinal cord. These inhibitions would lead to the shutting down of positive feedback between the bladder and the PMC, resulting in inhibition of the micturition reflex. Based on the central neural mechanisms we show here, gentle perineal stimulation may be applicable to several different types of overactive bladder.     

Amitriptyline and Imipramine Poisoning in Children

The increasing number of children admitted to this hospital with poisoning by tricyclic antidepressants is causing concern. Of 60 children admitted between January 1966 and July 1973, half were admitted in the last 18 months. In 60% of these patients the tricyclic compounds had been prescribed for nocturnal enuresis. One child aged 2 years and 4 months died of imipramine poisoning. It is imperative that all children with poisoning by tricyclic compounds, irrespective of the dosage, are admitted to hospital for continuous cardiac monitoring. Cardiac arrhythmias induced in children by amitriptyline and imipramine are prominent and dangerous.In the earlier years of this survey the antidepressants taken by children had usually been prescribed for adults, but recently they have been increasingly prescribed as a treatment for enuresis in children themselves. Medicine for a trivial complaint is unlikely to be regarded by parents as potentially dangerous and practitioners should therefore warn them accordingly; if, indeed, the transient effect of these potentially dangerous drugs upon the average case of bed-wetting in childhood can be justified.     

Age-related changes in urethrovesical coordination in male rats: relationship with bladder instability?

The micturition profile in conscious animals and the urethrovesical coordination in anesthetized conditions were investigated in 6- and 24-mo-old male Sprague-Dawley rats. The in vitro pharmacological responses to KCl, electrical field stimulation (EFS), carbachol, phenylephrine, and isoprenaline were determined in the isolated bladder body, the bladder neck, and urethra. A morphometric and immunohistological study has been included. During conscious cystomanometry, 63% of the aging rats but only 25% of the adult rats showed spontaneous contractions during the bladder-filling phase. In conscious aging rats, basal pressure, threshold pressure, and micturition pressure were also significantly increased. In anesthetized aging rats, a decrease in resting urethral pressure at micturition threshold and the occurrence of a significant delay in urethral relaxation during micturition were associated with an increased residual volume. In all isolated tissues, contractile response to KCl was not modified with aging, whereas age-related decreases in maximal responses to carbachol in the bladder body and to phenylephrine and carbachol in the urethra were observed. In the bladder neck only, we found a significant decrease in the amplitude of neurogenic contractions associated with fibrosis but without decrease in nerve density. These experiments show significant modifications in the voiding pattern of aging rats associated with urethral dysfunction and with regionally specific pharmacological and structural changes of the urinary tract. We propose that aging in rats is characterized by an impairment of the urethrovesical coordination, leading to bladder dysfunctions similar to those induced by bladder outlet obstruction.     

Effect of the NK-1 receptor antagonist GR 82,334 on reflexly-induced bladder contractions.

The effect of intrathecal administration of the novel tachykinin NK-1 receptor antagonist GR 82,334 has been tested in three reflexes which excite urinary bladder motility. GR 82,334 at 1 but not at 0.1 nmol/rat blocked the chemonociceptive micturition reflex induced by the topical application of capsaicin (4 micrograms/50 microliters) onto the urinary bladder. At the same dose proven effective in the chemonociceptive reflex, GR 82,334 did not affect either micturition reflex induced by bladder filling or the urinary bladder contraction induced by perineal pinching. These results suggest that, in urethane-anesthetized rats, specific stimuli applied in the periphery activate NK-1 receptors at spinal cord level facilitating urinary bladder reflex contractions.     

Effects of WAY100635, a selective 5-HT1A-receptor antagonist on the micturition-reflex pathway in the rat

5-Hydroxytryptamine (5-HT) receptors in the central nervous system have been implicated in the control of micturition. The present study was undertaken to evaluate the effects of a selective 5-HT1A-receptor antagonist [N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY100635)] on the micturition-reflex pathway in urethane-anesthetized female Wistar rats. Rhythmic isovolumetric bladder contractions evoked by bladder distension were abolished by 0.3- to 3-mg/kg iv or 30- to 100-microg intrathecal (it) administration of WAY100635 in a dose-dependent manner for periods of 3-15 min. Intrathecal injection of WAY100635 was effective only if injected at the L6-S1 spinal cord level, but not at the thoracic or cervical cord levels. WAY100635 (30-100 microg it) significantly reduced the amplitude of bladder contractions evoked by electrical stimulation of the pontine micturition center. However, the field potentials in the rostral pons evoked by electrical stimulation of pelvic nerve were not affected by intrathecal or intravenous injection of WAY100635. These results suggest that 5-HT1A receptors at the L6-S1 level of the spinal cord have an important role in the tonic control of the descending limb of the micturition-reflex pathway in the rat.     

Diurnal Variation in Urodynamics of Rat

In humans, the storage and voiding functions of the urinary bladder have a characteristic diurnal variation, with increased voiding during the day and urine storage during the night. However, in animal models, the daily functional differences in urodynamics have not been well-studied. The goal of this study was to identify key urodynamic parameters that vary between day and night. Rats were chronically instrumented with an intravesical catheter, and bladder pressure, voided volumes, and micturition frequency were measured by continuous filling cystometry during the light (inactive) or dark (active) phases of the circadian cycle. Cage activity was recorded by video during the experiment. We hypothesized that nocturnal rats entrained to a standard 12:12 light:dark cycle would show greater ambulatory activity and more frequent, smaller volume micturitions in the dark compared to the light. Rats studied during the light phase had a bladder capacity of 1.44±0.21 mL and voided every 8.2±1.2 min. Ambulatory activity was lower in the light phase, and rats slept during the recording period, awakening only to urinate. In contrast, rats studied during the dark were more active, had a lower bladder capacities (0.65±0.18 mL), and urinated more often (every 3.7±0.9 min). Average bladder pressures were not significantly different between the light and dark (13.40±2.49 and 12.19±2.85 mmHg, respectively). These results identify a day-night difference in bladder capacity and micturition frequency in chronically-instrumented nocturnal rodents that is phase-locked to the normal circadian locomotor activity rhythm of the animal. Furthermore, since it has generally been assumed that the daily hormonal regulation of renal function is a major driver of the circadian rhythm in urination, and few studies have addressed the involvement of the lower urinary tract, these results establish the bladder itself as a target for circadian regulation.     

Recurrent urinary infections in girls: relation to enuresis

Maximum bladder capacities (MBC) have been studied in 89 girls receiving treatment for urinary infections at a time when the infection had been controlled. Fifty-six of the girls had been enuretic when first seen, 40 remained enuretic even when the infection had been cured. The MBC''s of the enuretic children were significantly smaller than those who were not or had not been enuretic. The enuresis and small bladder capacities were therefore not usually due to the urinary infection. It is concluded that in girls either enuresis predisposes towards the development of urinary infections, or that a common underlying pathology predisposes to both entities.     

A 型肉毒素膀胱内阻滞治疗女性膀胱过度活动症的临床效果观察

目的：探讨A 型肉毒素膀胱内阻滞治疗女性膀胱过度活动症的临床效果。方法：选择2010 年10 月至2012 年10 月,哈尔滨 医科大学附属第四医院泌尿外科收治的女性膀胱过度活动症患者24 例,随机分为治疗组和对照组,治疗组(A 组)选用国产A 型 肉毒素(衡力)100 IU 治疗,用10 mL 生理盐水稀释后,通过膀胱镜进行壁内注射;对照组(B 组)患者给予口服经典的抗胆碱制剂, 酒石酸托特罗定片,每天口服2 次,每次2 mg,疗程不少于6 周。于治疗前,治疗后1 周和4 周观察和比较两组患者的IPSS评分、 初尿意膀胱容量、最大膀胱容量。结果：与治疗前比较,A 组治疗后1 周,IPSS评分显著下降(P<0.05),初尿意膀胱容量及最大膀胱 容量显著上升(P<0.05),治疗后第2 周和第4 周均维持在相当水平,残余尿量第1 周未见明显下降(P>0.05),第4 周时与基线比较 下降明显(P<0.05);B组于治疗后第4 周时,以上三项指标与治疗前比较才有统计学差异(P<0.05),残余尿量在第1 周即有明显下 降(P<0.05),并且第4 周时仍维持第1 周水平(P>0.05)。此外,治疗后第1 周两组比较以上指标比较有统计学差异(P<0.05),而治疗 后第4 周无明显差异(P>0.05)。结论：经尿道膀胱壁内肉毒素A 注射和口服酒石酸托特罗定均是治疗女性膀胱过度活动症的有效 方法,但A 型肉毒素膀胱内注射起效更快,同时由于其接触性和直观性,疗效更确切。     

Value of adjuvant treatment with imipramine for lumbosacral pain syndrome]

The antidepressants have been reported to be effective in the treatment of many pain syndromes, for example headache and neuralgia. The pain of the study was to evaluate the effectiveness on small (75 mg per die) dose of imipramine administered additionally to the routine. Conservative treatment of patients with acute low back pain. The analysis of six different indices of improvement revealed, that the outcome of therapy in the group of 50 patients treated with imipramine was significantly better, than in comparable group treated routinely. The effect of imipramine have not been related to the occurrence of depression or to the other factors from anamnesis and physical examination influencing pain.