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.     

Pathogenesis and brain functional imaging in nocturnal enuresis: A review

Nocturnal enuresis is a common and distressing developmental disease, which may cause various degrees of psychosocial stress and impairment to self-esteem in affected children as well as agitation to their parents or caregivers. Nevertheless, the etiology and pathogenesis of nocturnal enuresis are not understood. Currently, nocturnal enuresis is generally considered a multifactorial disease associated with a complex interaction of somatic, psychosocial, and environmental factors. A variety of postulations have been proposed to explain the occurrence and progression of nocturnal enuresis, including hereditary aberration, abnormal circadian rhythm of antidiuretic hormone secretion during sleep, bladder dysfunction, abnormal sleep, difficulties in arousal, neuropsychological disorders, and maturational delays of the brain. In recent decades, the introduction of functional neuroimaging technologies has provided new approaches for uncovering the mechanisms underlying nocturnal enuresis. The main neuroimaging modalities have included brain morphometry based on structural magnetic resonance imaging (MRI), task-based and event-related functional MRI (fMRI), and resting-state fMRI. The relevant studies have indicated that nocturnal enuresis is associated with functional and structural alterations of the brain. In this review, we briefly summarized the popular hypotheses regarding the pathogenesis of nocturnal enuresis and the current progress of functional neuroimaging studies in examining the underlying mechanisms thereof.     

Nocturnal Enuresis: Comparison of the Effect of Imipramine and Dietary Restriction on Bladder Capacity

Fifty children with nocturnal enuresis have been studied with a view to determining maximum bladder capacities and frequency of micturition, and the changes induced by dietary treatment and imipramine. Of 50 children treated with imipramine, 31 were symptomatically cured. Fifteen of the 48 children treated by dietary measures were also symptomatically cured, but as nine had already been cured by imipramine the correct cure rate for dietary treatment, for reasons indicated in the text, may have been no more than seven of the 48 cases. Treatment on the above lines, in those who responded, led to an increase in bladder capacity and a fall in diurnal frequency of micturition.Because the bladder can enlarge under the above conditions it is concluded that the bladder in the average enuretic is functionally but not structurally small, and that when dietary manipulation helps, it does so by eliminating factors from the diet to which the bladder is sensitive. Imipramine, by contrast, is effective because it blocks peripherally this effect.     

A controlled study of Tourette syndrome. VI. Early development, sleep problems, allergies, and handedness.

Developmental milestones, problems with bladder and bowel control, sleep disturbances, allergies, and handedness were compared in 247 consecutive Tourette syndrome (TS) patients, 17 patients with attention-deficit disorder (ADD), 15 patients with ADD secondary to TS (ADD 2(0) TS), and 47 random controls. There were no significant differences in age of first talking or walking. By contrast, there were significant differences in problems with bladder and bowel control between TS patients and controls, as measured by age of first toilet training, age of last bed-wetting, frequency of enuresis, and age that bowel control was achieved. Sleep problems were pervasive in TS patients, with a significantly increased frequency of sleepwalking, night terrors, trouble getting to sleep, early awakening, and inability to take afternoon naps as a young child. In all diagnostic categories, including mild (grade 1) TS patients, a total sleep-problem score was significantly greater than that in controls. The sleep disorders and other TS symptoms are consistent with TS as a disorder of disinhibition of the limbic system. Allergies and left-handedness have been evoked as contributing to or being associated with ADD and learning disorders. There were no significant differences in the frequency of allergies or left-handedness in TS patients compared with that in controls. We conclude that when there is a clearly defined genetic cause of ADD and learning disorders, it is not associated with an increased frequency of allergies or left-handedness.     

Persistent primary enuresis: a urodynamic assessment.

Videocystourethrography with synchronous pressure and flow-rate recordings has been carried out on 50 patients referred for the investigation of persistent primary enuresis. Urodynamic studies showed nocturnal enuresis to be associated mainly with normal detrusor function and nocturnal plus diurnal enuresis mainly with abnormal detrusor function. Evidence is presented which suggests that these two distinct types of enuresis occur de novo and do not overlap. Out of 18 of formerly enuretic male patients nine with abnormal detrusor function showed persistent nocturnal plus diurnal symptoms.     

The influence of the sleep-wake cycle on primary monosymptomatic nocturnal enuresis: a non-randomized comparative study

Backround: Enuresis implies severe stress in affected children, and impairs quality of life and sleep. Children with enuresis experience difficulties in their arousal from sleep, possibly associated with disturbances of the circadian rhythm. In this study, we aimed to evaluate the sleep–wake cycle and sleep disturbances in children with monosymptomatic enuresis nocturna (MEN). Method: The study comprised 70 children with MEN who were admitted to the pediatrics and urology outpatients department and 94 age-matched healthy controls. Parents completed “Strengths and Difficulties Questionnaire,” Children’s Sleep Habits Questionnaire (CSHQ), Children’s Chronotype Questionnaire scale. Results: Children with enuresis had significantly more sleep and psychological problem. Enuresis group reported higher bedtime resistance, parasomnias, breathing-related problems, and daytime sleepiness in CHSQ (p < 0.05). Although circadian preference did not differ statistically between the groups (p > 0.05), sleep duration on school days and awakening and mid-sleep points, both on scheduled and free days, were found to be significantly different in the enuretic group (p < 0.05). In logistic regression analysis, age, sleep period on scheduled days, sleep inertia on scheduled and free days were significant predictor for enuresis. Discussion: Children with enuresis were more likely to experience problematic sleep. This may reflect that enuretic children have impaired sleep–wake cycles, leading to dysregulation of daily functional changes of bladder capacity and related hormones such as ADH. These findings might imply a sleep–wake disturbance in enuresis.     

Construction and application of urinary system model with functional bladder module

In order to study the construction and application of urinary system model with functional bladder module, bladder model was designed, and appropriate materials was selected to make it, and its performance was studied. The results showed that in the analysis of pressure performance of bladder model, more detrusor instability was found in the model than in the urodynamic test, and there was significant statistical difference (P < 0.01). In the analysis of bladder safety capacity, it was found that the bladder safety capacity in the model was much larger than that measured by urodynamics, and there was significant statistical difference (P < 0.01). In the analysis of detrusor workmanship and contraction rate, it was found that the normal model group was significantly smaller than the obstruction group, and there was significant statistical difference (P < 0.01). Comparing the detrusor contraction rate of the two groups, it was found that the normal group and the obstruction group had significant difference at t3, and there was no statistical difference between the other two groups. Therefore, through this study, it is found that the understanding of urinary system can be enhanced by building bladder model, and the basic operating skills of medical staff can be improved more easily by using bladder model, which achieves the expected results of the experiment. Although some shortcomings have been found in the course of the study, it still provides experimental reference for the clinical study of bladder in the future.     

Urodynamic findings in chronic retention of urine and their relevance to results of surgery.

Fifty-five consecutive male patients aged 18-77 with chronic retention of urine were investigated urodynamically. All were shown to have obstructed micturition. Inflow cystometry defined two groups, one with high-pressure and one with low-pressure filling. Recent-onset enuresis and upper-tract dilatation as seen on radiography were significantly associated with high-pressure bladder filling. Postoperative studies showed that patients with high-pressure filling on preoperative cystometryhad a better response to outflow-tract surgery. The poor response of the patients with low-pressure filling was due to a high incidence of inadequate detrusor contraction leading to persistent residual urine. Thus urodynamic studies may be used to indicate which patients are likely to benefit from prostatectomy and, after the operation, whether the obstruction has been relieved.     

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.     

A comparative study of the affinities of some tricyclic antidepressants for the muscarinic cholinergic receptor in human and guinea-pig bladder, ileum and brain in relation to differential drug potency

Following a report that nortriptyline was found useful in the control of enuresis in adults, presumably as an anticholinergic, its likely mechanism of action and apparent bladder specificity have now been investigated in vitro. The ratios of anticholinergic potencies (reciprocal of dissociation contents, Ki) for four different tricyclic antidepressants, derived from competitive binding assays with (-)[3H]QNB in tissue homogenates, in the order (human) detrusor muscle/ileal longitudinal muscle/caudate, are as follows: Nortriptyline, 5/4/7; desipramine, 2/1/5/; clomipramine, 4/3/27; amitriptyline, 25/14/56. The apparent selective effect of nortriptyline on the bladder cannot be ascribed to its higher affinity to bladder receptors. Still, this drug is the least discriminatory of the four. Hence, at a given concentration, it is expected to affect tissue embodying a low density receptor pool sooner than tissue having a large receptor reserve. The ratios of the densities of (-)[3H]QNB binding sites in the order detrusor muscle/ileal muscle/cortex is 1/3/5, supporting the present contention. In the guinea-pig, the ratios of the anticholinergic potency in the order bladder/proximal ileum/distal ileum/cortex are as follows: Nortriptyline, 25/5/6/33; desipramine, 8/2/2/14; amitriptyline, 100/14/20/100; clomipramine, 17/3/5/33. Also, the ratios of the densities of binding sites are 1/6/5/2. Hence, data derived from assays in the guinea-pig are not representative of those derived from human tissue.     

The Practitioner and School Age Child Problems

The extraordinary plasticity of the growing child offers the general practitioner an unusual opportunity to intervene either in a preventative or therapeutic manner. Such intervention, properly the task of any informed physician dealing with families, can alter unhealthy growth to healthier development. The whole child is just as important as his medical illnesses; the whole family usually needs help when there is an emotional disturbance in any child.Common problems that lend themselves readily to physician intervention are behavior disorders accompanying a neurological deficit, conduct disorders, enuresis and school phobias. Knowing how to elicit information, to evaluate clinical data and to utilize the findings of a skilled psychologist, and when to refer to a psychiatrist, plus a thorough knowledge of community resources are part and parcel of a physician''s equipment for dealing with children and families.     

Urinary Bladder Dysfunction in Transgenic Sickle Cell Disease Mice

Background

Urological complications associated with sickle cell disease (SCD), include nocturia, enuresis, urinary infections and urinary incontinence. However, scientific evidence to ascertain the underlying cause of the lower urinary tract symptoms in SCD is lacking.

Objective

Thus, the aim of this study was to evaluate urinary function, in vivo and ex vivo, in the Berkeley SCD murine model (SS).

Methods

Urine output was measured in metabolic cage for both wild type and SS mice (25-30 g). Bladder strips and urethra rings were dissected free and mounted in organ baths. In isolated detrusor smooth muscle (DSM), relaxant response to mirabegron and isoproterenol (1nM-10μM) and contractile response to (carbachol (CCh; 1 nM-100μM), KCl (1 mM-300mM), CaCl₂ (1μM-100mM), α,β-methylene ATP (1, 3 and 10 μM) and electrical field stimulation (EFS; 1-32 Hz) were measured. Phenylephrine (Phe; 10nM-100μM) was used to evaluate the contraction mechanism in the urethra rings. Cystometry and histomorphometry were also performed in the urinary bladder.

Results

SS mice present a reduced urine output and incapacity to produce typical bladder contractions and bladder emptying (ex vivo), compared to control animals. In DSM, relaxation in response to a selective β3-adrenergic agonist (mirabegron) and to a non-selective β-adrenergic (isoproterenol) agonist were lower in SS mice. Additionally, carbachol, α, β-methylene ATP, KCl, extracellular Ca²⁺ and electrical-field stimulation promoted smaller bladder contractions in SS group. Urethra contraction induced by phenylephrine was markedly reduced in SS mice. Histological analyses of SS mice bladder revealed severe structural abnormalities, such as reductions in detrusor thickness and bladder volume, and cell infiltration.

Conclusions

Taken together, our data demonstrate, for the first time, that SS mice display features of urinary bladder dysfunction, leading to impairment in urinary continence, which may have an important role in the pathogenesis of the enuresis and infections observed the SCD patients.     

Functional bladder capacity and urodynamics in males with nocturia

Previous studies in males with lower urinary tract symptoms (LUTS) have shown that nocturia in some patients is associated with nocturnal polyuria whereas other patients have preserved circadian urine output rhythm. This outpatient study based on 7-dayss frequency/volume (FV) charts showed that patients with nocturnal polyuria and age-matched controls without nocturia had a diurnal variation in functional bladder capacity (FBC) with higher night-time values. In contrast, patients without nocturnal polyuria no diurnal variation was observed in FBC with lower day and night-time values than both controls and nocturnal polyuric patients. Nocturia volumes correlated significantly to daytime FBC in both patient groups. Voided volumes obtained from daytime pressure/flow urodynamic investigations correlated significantly with night-time FBC obtained from the FV chart. In patients with LUTS nocturia was caused by nocturnal polyuria in 10 of 23 patients and by diminished night-time functional bladder capacity in the remaining 13 patients. In conclusion, nocturia in males with LUTS referred for BPH evaluation is caused by a mismatch between nocturnal urine production and night-time FBC analogous with the pathophysiology of nocturnal enuresis. The evaluation of circadian urine production and FBC seems mandatory in the assessment of patients with nocturia and LUTS.     

Medical therapy for benign prostatic hyperplasia: new terminology, new concepts, better choices

This article discusses 3 areas of medical therapy for benign prostatic hyperplasia (BPH) that are undergoing extensive research and evaluation: 1) the use of muscarinic receptor antagonists to treat lower urinary tract symptoms (LUTS) in men with BPH; 2) the definition of an "enlarged prostate"; and 3) sexual function and LUTS. Fears of worsening obstructive symptoms or causing acute urinary retention often keep practitioners from prescribing muscarinic receptor antagonists to men who might have concomitant bladder outlet obstruction; a multicenter, multinational, double-blind study showed that tolterodine is safe for men with low postvoid residual volumes. Most urologists accept that a prostate volume of more than 40 mL is consistent with an enlarged prostate; there is more debate regarding prostate volumes of 30 to 40 mL. Recently presented data suggest that combination medical therapy might be effective for men having prostates with volumes of more than 25 mL. The association between voiding and sexual function has been increasingly recognized and investigated, and there seem to be common pathophysiologic mechanisms governing both conditions. Targeted treatment algorithms addressing both conditions seem warranted.     

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.     

EMG biofeedback for functional bladder-sphincter dyssynergia: A case study

The present study utilized EMG biofeedback in the treatment of functional bladder-sphincter dyssynergia, a learned incoordination of bladder and urethral sphincter activity during voiding. The condition is usually associated with a history of painful urination due to bladder infections, surgery, or harsh toilet training. The subject was an 8-year-old girl with chronic diurnal urinary frequency, urge incontinence, and nocturnal enuresis. Treatment consisted of intensive instruction in alternately tensing and relaxing her lower pelvic musculature, as well as relaxing during voiding. These exercises were accompanied by EMG biofeedback from perianal and perivaginal surface electrode sites. Home practice consisted of the tense-relax exercise, relaxation during voiding, and self-monitoring and record-keeping. There were 17 sessions over a period of 9 months. No medication was used. Marked reduction (to normal levels) in diurnal urgency and frequency occurred by the 3rd week of therapy, and complete recovery of normal function, including nocturnal continence without waking, occurred by the 13th therapy session, 5 months after therapy began. Follow-up 1 year after therapy revealed that these gains were being maintained. Pre- and posttherapy urodynamic studies corroborated the achievement of normal urinary function.     

Cell signaling in interstitial cystitis/painful bladder syndrome

Evidence for several types of cell signaling abnormalities has been presented for patients with interstitial cystitis/painful bladder syndrome (IC/PBS), a poorly understood chronic painful bladder disorder for which currently there is no reliable effective therapy. Increases or decreases in various urine cytokines and growth factors have been found in patient specimens, along with abnormal expression of epithelial differentiation markers, growth factors, cell membrane proteins, neurotransmitters, and other cytokines in tissue biopsies and/or explanted bladder cells from IC/PBS patients. Some of the abnormalities found in bladder epithelial cells from IC/PBS patients have been shown to be induced in normal cells by an antiproliferative factor from IC/PBS bladder epithelial cells that binds to a functional cell membrane receptor (CKAP4/p63). Greater understanding of cell signaling events associated with this debilitating disorder may lead to the development of more effective therapies.     

Sleep Cystometrography: A Preliminary Study of Bladder Function During Sleep

Bladder function during sleep was studied by the use of a cystometer which recorded detrusor contractions and intravesical pressure as urine accumulated in the bladder during diuresis. The cystometrographic tracing was obtained while the patient was awake. A detrusor contraction can occur during sleep. Results of such studies on five patients are presented, with photographs of representative cystometrographic tracings.The general pattern of the cystometrogram during sleep was found to be different from that obtained while the patient was awake. A detrusor contraction can occur during sleep and may subsequently: (a) subside without awakening the patient; (b) be associated with the involuntary escape of urine or flatus; or (c) cause the patient to awaken. It is suggested that detrusor contractions rather than increases in urinary volume are responsible for the individual''s awakening at night to urinate.In the light of these observations, further study of patients with enuresis and those with non-obstructive nocturia is required.     

Genetic and epigenetic aspects of bladder cancer

Transitional cell carcinoma of the urinary bladder has a diverse collection of biologic and functional characteristics. This is reflected in differing clinical courses. The diagnosis of bladder cancer is based on the information provided by cystoscopy, the gold standard in combination with urinary cytology findings. Many tumor markers have been evaluated for detecting and monitoring the disease in serum, bladder washes, and urinary specimens. However, none of these biomarkers reported to date has shown sufficient sensitivity and specificity for the detection of the whole spectrum of bladder cancer diseases in routine clinical practice. The limited value of established prognostic markers requires the analysis of new molecular parameters of interest in predicting the prognosis of bladder cancer patients; in particular, the high-risk patient groups at risk of progression and recurrence. Over the past decade, there has been major progress elucidating of the molecular genetic and epigenetic changes leading to the development of transitional cell carcinoma. This review focuses on the recent advances of genetic and epigenetic aspects in bladder cancer, and emphasizes how molecular biology would be likely to affect the future therapies.