Carlos Fernandes da Silva

Snoring in Portuguese Primary School Children

Objective. To determine the prevalence of snoring and its potential associations with sleep problems, such as daytime symptoms, medical conditions, school performance, and behavioral disturbances in Portuguese children attending primary school. Methods. A previously validated questionnaire was sent to the parents of 1381 children attending primary schools in a parish of Coimbra, Portugal. To assess behavioral disturbances, the Portuguese version of Rutters Childrens Behavior Questionnaire for completion by teachers was used. Results. Of the 988 questionnaires returned (71.5%), complete information concerning snoring was obtained for 976 children (496 girls and 480 boys; mean age: 8.1 ± 1.5 years). Loud snoring during sleep was reported as frequent or constantly present (LSn) in 84 children (8.6%), as occasionally present in 299 children (30.6%), and as never present (NSn) by 593 children (60.8%). The LSn and NSn groups did not differ with respect to age, gender, sleep duration, time to fall asleep, frequency of night wakings, bedwetting, daytime tiredness, and school achievement. However, LSn was significantly associated with increased bedtime problems (fears and struggles), increased need for comforting activities to fall asleep, behaviors suggestive of parasomnias (sleep talking, teeth grinding, and night terrors), increased daytime sleepiness and irritability, and behavioral disturbances. Children in the LSn group were also more likely to report recurrent medical problems particularly those involving infections of the respiratory tract. Conclusions. Snoring is a common symptom in Portuguese children that is associated with behavioral daytime and sleep time disturbances. Children with loud snoring may benefit from early evaluation and intervention.

The Effect Of Intravesical Resiniferatoxin In Patients With Idiopathic Detrusor Instability Suggests That Involuntary Detrusor Contractions Are Triggered By C-Fiber Input

PURPOSE We evaluated the role of bladder C-fiber input in involuntary detrusor activity in patients with idiopathic detrusor instability. MATERIALS AND METHODS Filling cystometry and a voiding chart were done in 13 patients with idiopathic detrusor instability. The first detrusor contraction, maximal cystometric capacity, daily frequency and the number of episodes of urinary incontinence were determined. A 50 nM. solution of resiniferatoxin, a specific C-fiber neurotoxin, was then instilled in the bladder for 30 minutes. Patients were reevaluated 30 and 90 days later. RESULTS Resiniferatoxin instillation delayed or suppressed involuntary detrusor contractions during filling cystometry. The mean first detrusor contraction plus or minus standard deviation increased from 170 +/- 109 ml. at baseline to 440 +/- 130 ml. (p = 0.0001) at 30 days and to 391 +/- 165 ml. (p = 0.008) at 90 days. Mean maximal cystometric capacity increased from 291 +/- 160 to 472 +/- 139 ml. (p = 0.01) at 30 days and to 413 +/- 153 ml. (p = 0.1) at 90 days. The mean number of episodes of urinary incontinence daily decreased from 4.3 +/- 2.7 to 0.9 +/- 2.7 (p = 0.001) at 30 days and to 0.7 +/- 0.9 (p = 0.009) at 90 days. Mean frequency daily also decreased from 12 +/- 3.2 to 9.7 +/- 3.2 (p = 0.003) and to 9.9 +/- 3.5 (p = 0.001) times at the same time points, respectively. CONCLUSIONS C-fiber input seems to have an important role in the generation of involuntary detrusor contractions and lower urinary tract symptoms in patients with idiopathic detrusor instability. Substances that block C-fiber input may represent a new strategy for treating this bladder dysfunction.

DESENSITIZATION OF BLADDER SENSORY FIBERS BY INTRAVESICAL CAPSAICIN HAS LONG LASTING CLINICAL AND URODYNAMIC EFFECTS IN PATIENTS WITH HYPERACTIVE OR HYPERSENSITIVE BLADDER DYSFUNCTION

PURPOSE Capsaicin was used to treat symptomatic patients with hyperactive or hypersensitive bladders. MATERIALS AND METHODS Capsaicin solution (1 mM.) was instilled into the bladder of 16 patients with spinal hyperreflexia, bladder instability or hypersensibility. RESULTS Frequency decreased in 14 patients and continence was achieved in 10 of 14 incontinent cases. Mean first desire to void and maximal cystometric capacity increased significantly. These effects lasted for 6 to 12 months and were renewed following repeat treatment. CONCLUSIONS Bladder afferent desensitization with capsaicin is promising in patients with motor or sensory bladder dysfunction, although initial pungency might limit its use.

Desensitization of Bladder Sensory Fibers by Intravesical Resiniferatoxin, a Capsaicin Analog: Long–Term Results for the Treatment of Detrusor Hyperreflexia

Objectives: To assess the pungency and the desensitizing effects of intravesical resiniferatoxin, an ultrapotent capsaicin analog, in patients with detrusor hyperreflexia.Methods: Fourteen patients with detrusor hyperreflexia were instilled during 30 min, without any form of local anesthesia, with 100 ml (or the bladder capacity if lower than that volume) of 50 or 100 nM resiniferatoxin solutions in 10% alcohol in saline. Patients were evaluated by voiding chart and urodynamic tests (volume to first contraction, maximal cystometric capacity, maximal detrusor pressure, icewater test) at 14, 30, 60, and 90 days and every 3 months thereafterResults: Resiniferatoxin instillation did not evoke pain or temporary worsening of urinary symptoms. Treatment improved or abolished incontinence in 9 out of 12 incontinent patients. Mean urinary frequency decreased from 14.2±6.4 to 10.3±3.2 at 3 months (p = 0.01). At this time point, mean maximal cystometric capacity increased from 182.3±119.8 to 330.0±201.6 ml (p = 0.01) and the ice water test, positive in 13 cases, became negative in 8 of them. Maximal detrusor pressure was not modified by the treatment. The effect was long–lasting, reaching 12 months in 7 cases.Conclusions: The absence of irritative symptoms during bladder instillation of resiniferatoxin and the rapid onset of desensitization make this vanilloid superior to capsaicin for the treatment of detrusor hyperreflexia.

Distribution of the High-Affinity Binding Site and Intracellular Target of Botulinum Toxin Type A in the Human Bladder

BACKGROUND Botulinum toxin type A (BoNTA) has been successfully used in the treatment of refractory detrusor overactivity. The toxin is internalized after binding a high-affinity receptor, synaptic vesicle protein 2 (SV2), which is exposed in the cell membrane during the exocytosis process. In the cytoplasm, BoNTA cleaves specific sites of synaptosomal-associated protein 25 (SNAP-25), preventing the assembly of the synaptic fusion complex SNARE and blocking exocytosis. OBJECTIVE In the present work, the distribution of SV2 and SNAP-25 was first investigated in human bladders. The neurochemistry of BoNTA-sensitive structures was then investigated using markers for parasympathetic, sympathetic, and sensory fibers. DESIGN, SETTING, AND PARTICIPANTS Human bladders were obtained from cadaveric organ donors (age range: 19-74 yr). MEASUREMENTS Bladder sections were processed for single or dual immunofluorescence staining with antibodies against SV2, SNAP-25, β-3 tubulin, vesicular acetylcholine transporter, tyrosine hydroxilase, and calcitonin gene-related peptide. RESULTS AND LIMITATIONS SV2 and SNAP-25 immunoreactive fibers were distributed throughout the suburothelium and muscular layer. Double labeling showed extensive colocalization of both proteins in nerve fibers. SV2 is more expressed in parasympathetic fibers than in sympathetic or sensory fibers. No expression was found in urothelial or muscular cells. Because only normal bladders were used, this distribution should be applied with caution to pathologic bladders. CONCLUSIONS SV2 and SNAP-25 colocalize abundantly throughout the urinary bladder. SV2 is more abundant in cholinergic, parasympathetic fibers. These nerves are suggested to be the main target for BoNTA action in the human urinary bladder.

Exploratory Study Assessing Efficacy and Complications of TVT-O, TVT-Secur, and Mini-Arc: Results at 12-Month Follow-Up

BACKGROUND Contemporary surgical treatment of female stress urinary incontinence (SUI) includes retropubic and transobturator (TO) midurethral slings (MUS). Case series of single-incision slings (SIS) have shown similar outcomes with lower morbidity. OBJECTIVE Our aim was to assess the cure rates, complications, and quality-of-life impact of one standard TO MUS and two SIS. DESIGN, SETTING, AND PARTICIPANTS Ninety consecutive patients with clinically and urodynamically proven SUI were enrolled in an exploratory randomised phase 2 trial. Patients with previous SUI surgery, major pelvic organ prolapse, mixed incontinence, or detrusor overactivity were excluded. INTERVENTIONS Patients were treated randomly with TVT-O, TVT-Secur, or Mini-Arc. MEASUREMENTS Postoperative visits were scheduled at 6 and 12 mo. The Kings Health Questionnaire (KHQ) was repeated at 6 mo. Cure was defined as the absence of urine leakage, no pad use, and a negative cough test at 12 mo. Pain and other complications were also investigated. RESULTS AND LIMITATIONS Cure rate was 83% after TVT-O, 67% after TVT-Secur, and 87% after Mini-Arc. Improvement was found in 10%, 13%, and 7% of the patients, respectively. Failures were 7% after TVT-O and Mini-Arc and 20% after TVT-Secur. TVT-O and Mini-Arc improved at least 15 points in >80% of the patients in six KHQ domains, whereas TVT-Secur could only achieve improvement in three of the nine domains. The pain score was lower in the Mini-Arc group. Complications were more numerous after TVT-O. This study has the limitations inherent in a phase 2 trial with a follow-up limited to 12 mo. CONCLUSIONS Mini-Arc offers cure and improvement rates similar to TVT-O, whereas TVT-Secur may yield an inferior outcome. These findings recommend the urgent launch of large randomised phase 3 studies comparing conventional MUS with SIS, with Mini-Arc the advised option.

Bladder sensory desensitization decreases urinary urgency

BackgroundBladder desensitization has been investigated as an alternative treatment for refractory detrusor overactivity. Most open and controlled clinical trials conducted with intravesical RTX showed that desensitization delays the appearance of involuntary detrusor contractions during bladder filling and decreases the number of episodes of urgency incontinence.Urgency is being recognised as the fundamental symptom of overactive bladder (OAB), a symptomatic complex which recent epidemiological studies have shown to affect more than 10% of the Western population. As anti-muscarinic drugs, the first line treatment for OAB, are far from being able to fully control urgency, the opportunity to test other therapeutic approaches is created. The present work was, therefore, designed as an exploratory investigation to evaluate the effect of bladder desensitization on urinary urgency.MethodsTwenty-three OAB patients with refractory urgency entered, after given informed consent, a 30 days run-in period in which medications influencing the bladder function were interrupted. At the end of this period patients filled a seven-day voiding chart where they scored, using a 0–4 scale, the bladder sensations felt before each voiding. Then, patients were instilled with 100 ml of 10% ethanol in saline (vehicle solution) and 30 days later a second seven-day voiding chart was collected. Finally, patients were instilled with 100 ml of 50 nM RTX in 10% ethanol in saline. At 1 and 3 months additional voiding charts were collected.At the end of the vehicle and 3 months period patients were asked to give their subjective impression about the outcome of the treatment and about the willingness to repeat the previous instillation.ResultsAt the end of the run-in period the mean number of episodes of urgency per week was 71 ± 12 (mean ± SEM). After vehicle instillation, the mean number of episodes of urgency was 56 ± 11, but only 4 patients (17%) considered that their urinary condition had improved enough to repeat the treatment. At 1 and 3 months after RTX the number of episodes of urgency decreased to 39 ± 9 (p = 0.002) and 37 ± 6 (p = 0.02), respectively (p indicates statistical differences against vehicle). The percentage of patients with subjective improvement after RTX and willing to repeat the instillation at a later occasion was 69%.ConclusionIn OAB patients with refractory urgency bladder desensitization should be further investigated as an alternative to the standard management. Additionally, the specific effect of RTX on TRPV1 receptors suggests that urothelium and sub-urothelial C-fibers play an important role to the generation of urgency sensation.

Short-term assessment of a tension-free vaginal tape for treating female stress urinary incontinence

To evaluate the short‐term surgical complications and results of a tension‐free vaginal tape (TVT) system (TVT‐SecurTM, Gynecare, Ethicon, Somerville, NJ, USA) in the treatment of female stress urinary incontinence (SUI).

Adult attachment style and cortisol responses in women in late pregnancy

BackgroundRecent research has documented the association between attachment and cortisol rhythms. During pregnancy, when attachment patterns are likely to be activated, elevated levels of cortisol are associated with negative effects for the mother and the foetus. The aim of the present study was to examine the association of adult attachment style and cortisol rhythms in pregnant women.MethodsEighty women in the third trimester of pregnancy participated in the study. Adult attachment was assessed using the Adult Attachment Scale – Revised (AAS-R). Participants collected 4 samples of salivary cortisol at two different days; 3 samples were collected in the morning immediately after wakeup and one sample was collected by bedtime.ResultsResults found group significant differences in the cortisol diurnal oscillation (F(1,71) = 26.46, p < .001,), with secure women reporting a steep decrease in cortisol from awakening to bedtime, while women with fearful avoidant attachment reported no changes. No group differences were found regarding the cortisol awakening response.ConclusionsThese results highlight the importance of considering attachment patterns during pregnancy, suggesting fearful avoidant attachment style as a possible risk factor for emotional difficulties and dysregulation of the neuroendocrine rhythms.

A light‐ and electron‐microscopic histopathological study of human bladder mucosa after intravesical resiniferatoxin application

Objective To determine the morphology of bladder mucosa and the integrity of its mucin coat in patients with detrusor hyper‐reflexia treated with intravesical resiniferatoxin.