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Introduction: Ureteropelvic junction obstruction (UPJO) syndrome is one of the most common causes of neonatal hydronephrosis. Management varies from simple monitoring to surgical intervention, with indications differing between institutions. A consensus of 8 societies recently described a new Urinary Tract Dilation (UTD) classification which aims to standardize ultrasound description of hydronephrosis, but which is also supposed to have predictive value in children with hydronephrosis. Our aim was to compare, in a monocentric prospective cohort of children with UPJO, the ability of UTD to predict the occurrence of a clinically significant event within the first year of life, as compared to anteroposterior diameter of the renal pelvis (APD). Study design: We used a preexisting cohort of children followed in a prospective study on UPJO. A pediatric radiologist, blinded to the children's outcome, classified the last antenatal ultrasound and postnatal ultrasound according to the UTD-A and UTD-P classification. He also confirmed the APD-A and APD-P measures. We defined a clinically significant event as being: increased pelvic dilation (>5â mm) and/or the presence of a febrile urinary tract infection (fUTI) and/or impaired renal function on initial nuclear scan (<40%). We performed a ROC-AUC curve and Random Forest (RF) analysis to compare the ability of the APD-A, APD-P, UTD-A and UTD-P scores to predict a clinically significant event. Results: The cohort included 28 children. Clinically significant events were noted in 20 out of 28 patients: 13 children presented an increase >5â mm in dilation, 6 presented an episode of fUTI and 9 had impaired function of the affected kidney. APD-A was the most effective individual criterion for predicting the occurrence of a significant clinical event (AUC = 0.867). Conclusion: In our series, for children with UPJO, the most significant marker was prenatal APD >15â mm to predict an increase in dilation >5â mm.
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Introduction: Childhood chronic diseases affect family functioning and well-being. The aim of this study was to measure the impact of caring for a child with PUV, and the factors that most impact the burden of care. Patients and method: We gave a questionnaire on the familial impact of having a child with posterior urethral valves to all parents of a child included in the CIRCUP trial from 2015 onwards. The questionnaire included questions about the parents' demographics, health, professional, financial and marital status and how these evolved since the child's birth as well as the "impact on family scale" (IOFS), which gives a total score ranging from 15 (no impact) to 60 (maximum impact). We then analyzed both the results of the specific demographic questions as well as the factors which influenced the IOFS score. Results: We retrieved answers for 38/51 families (74.5% response rate). The average IOFS score was 23.7 (15-51). We observed that the child's creatinine level had an effect on the IOFS score (p = 0.02), as did the parent's gender (p = 0.008), health status (p = 0.015), being limited in activity since the birth of the child (p = 0.020), being penalized in one's job (p = 0.009), being supported in one's job (p = 0.002), and decreased income (p = 0.004). Out of 38 mother/father binomials, 8/33 (24.2%) declared that they were no longer in the same relationship afterwards. Conclusion: In conclusion, having a boy with PUV significantly impacts families. The risk of parental separation and decrease in revenue is significant. Strategies aiming to decrease these factors should be put in place as soon as possible.
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PURPOSE: OnabotulinumtoxinA is an approved treatment for neurogenic detrusor overactivity in adults inadequately managed with anticholinergics, and more recently was approved in children on the basis of a phase 3, 48-week, single-treatment study (NCT01852045). Given the paucity of long-term pediatric data, we report on the continued safety in these patients after repeated onabotulinumtoxinA treatment. MATERIALS AND METHODS: This was a multicenter, double-blind, repeat-treatment extension study (NCT01852058) in patients who entered from the preceding single-treatment study. Data were integrated across both studies. All patients (5-17 years) used clean intermittent catheterization and could receive dose escalations based on response to preceding treatment (50 U, 100 U, or 200 U onabotulinumtoxinA [not to exceed 6 U/kg]). RESULTS: Overall, 95, 90, 55, and 11 patients received 1, 2, 3, and 4 treatments with onabotulinumtoxinA, respectively, and median (quartiles) duration of follow-up was 82 (65, 94) weeks. The safety profile was similar across doses and after repeat treatments. The most common treatment-emergent adverse event during cycles 1, 2, and 3 was urinary tract infection (31%, 34%, 22%). Three serious treatment-emergent adverse events related to study treatment (3/95; 3.2%) were reported during the study, which were all cases of urinary tract infection. Annualized urinary tract infection rates post-treatment were similar to pre-screening rates. There were no cases of autonomic dysreflexia, neutralizing antibodies, and treatment-emergent adverse events related to distant spread of toxin. CONCLUSIONS: OnabotulinumtoxinA continued to be well tolerated after repeated treatments in pediatric neurogenic detrusor overactivity patients with similar safety profiles across dose groups. Treatment-emergent adverse events were primarily urological with no new safety concerns.
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Toxinas Botulínicas Tipo A , Vejiga Urinaria Neurogénica , Vejiga Urinaria Hiperactiva , Infecciones Urinarias , Adulto , Humanos , Niño , Resultado del Tratamiento , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Infecciones Urinarias/tratamiento farmacológico , Método Doble Ciego , Vejiga Urinaria Neurogénica/tratamiento farmacológicoRESUMEN
Objective: Boys with posterior urethral valves (PUV) present an increased risk of febrile urinary tract infection (fUTI). Identifying specific risk factors could allow for tailoring UTI prevention. The aim of this study was to use the data from the CIRCUP randomized controlled trial data to identify patient characteristics associated with a higher risk of fUTI. Patients and methods: We performed a secondary analysis of the data from the CIRCUP randomized trial which included boys with PUV, randomized to circumcision and antibiotic prophylaxis vs. antibiotic prophylaxis alone and followed for 2 years. There was only 1 episode of fUTI in the circumcision group vs. 17 in the uncircumcised group. We therefore only studied the antibiotic prophylaxis alone group and compared age at prenatal diagnosis, size and weight at birth, presence of dilating VUR at diagnosis, abnormal DMSA scan at 2 months, and nadir creatinine between children who presented a fUTI and those who did not, as well as age at first episode of fUTI. Results: The study group consisted of 42 patients of which 17 presented at least on fUTI. Presence of dilating VUR was significantly associated with risk of fUTI (p = 0.03), OR: 6 [CI 95% = (1.13-27.52)]. None of the other parameters were associated with increased risk of fUTI. We observed three distinct time periods for presenting a fUTI with a decrease in infection rate after the first 40 days of life, then at 240 days of life. Conclusion: In boys with PUV, presence of high-grade VUR is associated with a higher risk of presenting a fUTI. The rate of febrile UTIs seems to decrease after 9 months.
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OBJECTIVES: To describe our experience with prenatal counselling for surgical anomalies in a large volume center. The secondary aim is to suggest a list of prenatal abnormalities warranting counselling by a pediatric surgeon. METHODS: We reviewed all prenatal counselling consultations performed by the pediatric surgery team between January 1st, 2015 and December 31st, 2016. RESULTS: A total of 169 patients or couples had a prenatal consultation with a pediatric surgeon. Prenatal work-up included a fetal MRI in 26% of cases, mainly for digestive and thoracic pathologies (56.1% of cases). Consultation with the pediatric surgeon led mainly to recommendations concerning the place of delivery. Induction for reasons related to the fetal anomaly occurred in 22.2% of cases. Most children were surgically treated within the first year of life (63.5%). Correlation between predicted prognosis and actual status at four years of life was 96.9%. Correlation between prenatal and postnatal diagnosis was 87.4%. CONCLUSIONS: Prenatal counselling by a pediatric surgeon allows couples to obtain clear information on the pathology of their unborn child, giving them greater autonomy in their decision to continue the pregnancy.
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Diagnóstico Prenatal , Cirujanos , Femenino , Hospitales , Humanos , Embarazo , Derivación y Consulta , Atención Terciaria de Salud , Ultrasonografía PrenatalRESUMEN
Congenital abnormalities of the genitourinary tract are the most common sonographically identified malformations. Although prenatal diagnosis seldom modifies perinatal management, it can cause significant anxiety in parents. We aimed to assess how parents perceived the prenatal counseling they had received in our institution. Using a questionnaire, we evaluated by phone the mothers of 78 children diagnosed prenatally with urological tract anomalies between January 2018 and May 2019. Overall, mothers were satisfied and reassured by the prenatal counseling they received, although 19% of the mothers found the time from diagnosis to specialist consultation to be too long. Forty percent of the responders stated that the most important information they needed to hear during the specialist consultation was management and not diagnosis. Specialist counseling should focus on explaining postnatal management, should be offered as soon as possible, and should include practical aspects, especially concerning outpatient care.
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Anomalías Congénitas/diagnóstico , Madres/psicología , Percepción , Diagnóstico Prenatal/normas , Sistema Urinario/anomalías , Adulto , Anomalías Congénitas/psicología , Consejo/normas , Consejo/estadística & datos numéricos , Femenino , Humanos , Madres/estadística & datos numéricos , Embarazo , Atención Prenatal/psicología , Atención Prenatal/normas , Atención Prenatal/estadística & datos numéricos , Diagnóstico Prenatal/métodos , Diagnóstico Prenatal/estadística & datos numéricos , Sistema Urinario/fisiopatologíaRESUMEN
INTRODUCTION: Fibroepithelial polyps (FEP) of the lower urinary tract are relatively common in adults but rare in children, with fewer than 250 cases reported in the literature to date. OBJECTIVE: The aim of this study was to address the experience of FEP management in children. STUDY DESIGN: A retrospective multicenter review was undertaken in children with defined FEP of the lower urinary tract managed between 2008 and 2018. The data at 18 pediatric surgery centers were collected. Their demographic, radiological, surgical, and pathological information were reviewed. RESULTS: A total of 33 children (26 boys; 7 girls) were treated for FEP of the lower urinary tract at 13 centers. The most common presentation was urinary outflow as hematuria (41%), acute urinary retention (25%), dysuria (19%), or urinary infections (28%). A prenatal diagnosis was made for three patients with hydronephrosis. Almost all of the children (94%) underwent ultrasound imaging of the urinary tract as the first diagnostic examination, 23 (70%) of them also either had an MRI (15%), cystourethrography (25%), computerized tomography (6%), or cystoscopy (45%). Two of these children (6%) had a biopsy prior to the surgery. The median preoperative delay was 7.52 (range: 1-48) months. Most of the patients were treated endoscopically, although four (12.1%) had open surgery and two (6.1%) had an additional incision for specimen extraction. The median hospital stay was 1.5 (range: 1-10) days. There were no recurrences and no complications after a median follow-up of 13 (range: 1-34) months. DISCUSSION: The main limitation of our study is the retrospective design, although it is the largest one for this pathology. CONCLUSION: This series supports sonography as the most suitable diagnosis tool before endoscopy to confirm the diagnosis and to perform the resection for most FEP in children. This report confirms the recognized benign nature in the absence of recurrences. LEVEL OF EVIDENCE: Level V.
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Pólipos , Sistema Urinario , Adulto , Niño , Femenino , Humanos , Masculino , Recurrencia Local de Neoplasia , Pólipos/diagnóstico por imagen , Pólipos/cirugía , Estudios Retrospectivos , Vejiga UrinariaRESUMEN
AIMS: This study evaluated whether one (or more) of three doses of onabotulinumtoxinA were safe and effective to treat neurogenic detrusor overactivity (NDO) in children. METHODS: This was a 48-week prospective, multicenter, randomized, double-blind study in children (aged 5-17 years) with NDO and urinary incontinence (UI) receiving one onabotulinumtoxinA treatment (50, 100, or 200 U; not to exceed 6 U/kg). Primary endpoint: change from baseline in daytime UI episodes. Secondary endpoints: change from baseline in urine volume at first morning catheterization, urodynamic measures, and positive response on the treatment benefit scale. Safety was also assessed. RESULTS: There was a similar reduction in urinary incontinence from baseline to Week 6 for all doses (-1.3 episodes/day). Most patients reported positive responses on the treatment benefit scale (75.0%-80.5%). From baseline to Week 6, increases were observed in urine volume at first morning clean intermittent catheterization (50 U, 21.9 ml; 100 U, 34.9 ml; 200 U, 87.5 ml; p = 0.0055, 200 U vs. 50 U) and in maximum cystometric capacity (range 48.6-63.6 ml) and decreases in maximum detrusor pressure during the storage phase (50 U, -12.9; 100 U, -20.1; 200 U, -27.3 cmH2 O; p = 0.0157, 200 U vs. 50 U). The proportion of patients experiencing involuntary detrusor contractions dropped from baseline (50 U, 94.4%; 100 U, 88.1%; 200 U, 92.6%) to Week 6 (50 U, 61.8%; 100 U, 44.7%; 200 U, 46.4%). Safety was similar across doses; urinary tract infection was most frequent. CONCLUSIONS: OnabotulinumtoxinA was well tolerated and effective for the treatment of NDO in children; 200 U showed greater efficacy in reducing bladder pressure and increasing bladder capacity.
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Toxinas Botulínicas Tipo A/uso terapéutico , Vejiga Urinaria Neurogénica/tratamiento farmacológico , Adolescente , Toxinas Botulínicas Tipo A/farmacología , Niño , Preescolar , Método Doble Ciego , Femenino , Humanos , Masculino , Estudios Prospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: Endoscopic injection is an accepted alternative for the treatment of vesicoureteral reflux (VUR) with the most commonly used agent being dextranomer/hyaluronic acid (Dx/HA). There are few reports on very long-term results after this treatment, although the biodegradable nature of the product could indicate that results might deteriorate on the long term. We, therefore, decided to evaluate the efficacy of Dx/HA copolymer endoscopic injection, in terms of recurrence of febrile urinary tract infections (fUTIs) in children, with a follow-up of at least 10 years. MATERIALS AND METHODS: We analyzed the medical data of all children who were diagnosed with VUR and underwent endoscopic injection with >10 years follow-up, in two University Hospitals. We reviewed their medical files and then contacted patients by phone. RESULTS: We found 68 patients who had undergone endoscopic treatment of VUR with a follow-up of minimum 10 years. We were able to contact 53 of these patients of whom 38 were girls, and 36 had bilateral VUR with a total of 89 ureteral units. Mean age at surgery was 86 months (26-136). Mean follow-up was 12.5 years (range: 10.5-15). No child presented postinjection obstruction. Thirteen patients presented with a recurrence of fUTI during the postoperative course of whom 8 presented persistent VUR. All recurrences of fUTI occurred within the first 5 years of follow-up. Four underwent a second injection and 4 underwent open reimplantation. Success rate per patient was 85%. CONCLUSION: Results of endoscopic injection using Dx/HA remain stable over time (>10 years). In our series, recurrences of fUTI occur within the first 5 years of follow-up.
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Dextranos/administración & dosificación , Endoscopía/métodos , Ácido Hialurónico/administración & dosificación , Inyecciones/métodos , Procedimientos Quirúrgicos Urológicos/métodos , Reflujo Vesicoureteral/cirugía , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Masculino , Recurrencia , Reimplantación , Infecciones Urinarias/etiologíaRESUMEN
PURPOSE: While familial forms of complex disorders/differences of sex development have been widely reported, data regarding isolated hypospadias are sparse and a family history is thought to be less frequent. We aimed to determine the frequency of hypospadias in families of boys with hypospadias, to establish whether these familial forms exhibit a particular phenotype and to evaluate the prevalence of genetic defects of the main candidate genes. MATERIALS AND METHODS: A total of 395 boys with hypospadias were prospectively screened for a family history with a standardized questionnaire, extensive clinical description, family tree and sequencing of AR, SF1, SRD5A2 and MAMLD1. RESULTS: Family history of hypospadias was more frequent than expected (88 patients, 22.3%). In 17 instances (19.3%) familial hypospadias cases were multiple. Familial hypospadias was related to the paternal side in 59.1% of cases, consisting of the father himself (30.7%) as well as paternal uncles and cousins. Premature birth, assisted reproductive techniques, other congenital abnormalities and growth retardation were not more frequent in familial hypospadias than in sporadic cases. The severity of phenotype was similar in both groups. The results of genetic analysis combined with previous data on androgen receptor sequencing revealed that familial cases more frequently tend to demonstrate genetic defects than sporadic cases (5.68% vs 1.63%, p = 0.048). CONCLUSIONS: Familial forms of hypospadias are far more frequent than previously reported. Even minor and isolated forms justify a full clinical investigation of the family history. Detecting these hereditary forms may help to determine the underlying genetic defects, and may improve followup and counseling of these patients.
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Predisposición Genética a la Enfermedad/epidemiología , Hipospadias/epidemiología , Hipospadias/genética , Linaje , 3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/genética , Preescolar , Estudios de Seguimiento , Humanos , Incidencia , Lactante , Masculino , Tamizaje Masivo/métodos , Estudios Prospectivos , Receptores Androgénicos/genéticaRESUMEN
AIM: Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disorder. Malignant transformation into malignant peripheral nerve sheath tumors (MPNST) can occur. However, urinary tract involvement is rare. We report 4 cases of NF1 with bladder dysfunction. METHODS: A retrospective single center analysis of 4 patients was conducted over a 17-year period, focusing on urinary tract involvement. RESULTS: NF1 was diagnosed at a median of 16.5 months (4-36) and urinary involvement occurred at a median of 5.25 years (4-9) after diagnosis. Bladder dysfunction was due to spinal cord compression in 2 cases, bladder invasion in 1 case, and cerebral lesions in 1 case. Malignant transformation of neurofibromas into MPNST occurred in 2 patients. Mechanisms of urinary involvement in NF1 are diverse and no pre-established protocol of management and follow-up exists. CONCLUSION: Although rare, dysfunction of the bladder can arise in NF1 and innovative strategies then need to be considered. This is best achieved with the help of a multidisciplinary team and a national reference center when available.
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Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/diagnóstico , Enfermedades de la Vejiga Urinaria/complicaciones , Enfermedades de la Vejiga Urinaria/diagnóstico , Vejiga Urinaria/fisiopatología , Adolescente , Neoplasias Encefálicas/complicaciones , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Neurofibromatosis 1/patología , Neurofibrosarcoma/complicaciones , Neurofibrosarcoma/diagnóstico , Estudios Retrospectivos , Compresión de la Médula Espinal/complicaciones , Enfermedades de la Vejiga Urinaria/patología , Incontinencia Urinaria/complicaciones , Incontinencia Urinaria/diagnóstico , Retención Urinaria/complicaciones , Retención Urinaria/diagnósticoAsunto(s)
Ansiedad , Educación en Salud/métodos , Padres , Procedimientos Quirúrgicos Operativos , Ansiedad/etiología , Ansiedad/prevención & control , Niño , Humanos , Padres/educación , Padres/psicología , Periodo Preoperatorio , Procedimientos Quirúrgicos Operativos/educación , Procedimientos Quirúrgicos Operativos/psicologíaAsunto(s)
Enfermedades del Recién Nacido , Vómitos , Niño , Humanos , Lactante , Recién Nacido , Vómitos/diagnóstico , Vómitos/etiologíaRESUMEN
OBJECTIVE: Prenatal management of male fetuses with suspected posterior urethral valves depends on reliable markers for postnatal long-term renal function. Whether ultrasound parameters, including the presence or absence of oligohydramnios, are reliable remains the subject of debate. We decided to evaluate the reliability of quantity of amniotic fluid to predict postnatal renal function using decision curve analysis (DCA), a method for evaluating the clinical utility of a diagnostic test. METHODS: We analyzed retrospectively 51 male fetuses born with prenatally suspected posterior urethral valves between 2009 and 2012. We studied the relationship between quantity of amniotic fluid on prenatal ultrasound and the nadir creatinine during the first year of life as a proxy of postnatal renal function using DCA. RESULTS: Twelve fetuses presented with prenatal oligohydramnios. Thirty-one children had a normal nadir creatinine, of which one had prenatal oligohydramnios (3.2%). Thirteen had a nadir creatinine between 35 and 75 µmol/L, of which four had prenatal oligohydramnios (30.8%). Seven had a nadir creatinine >75 µmol/L, all of them had prenatal oligohydramnios. CONCLUSION: In this retrospective study, DCA confirms the relationship between prenatal quantity of amniotic fluid volume and postnatal renal function. © 2017 John Wiley & Sons, Ltd.
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Líquido Amniótico/diagnóstico por imagen , Enfermedades Renales/diagnóstico , Riñón/fisiopatología , Ultrasonografía Prenatal , Uretra/anomalías , Creatinina/sangre , Técnicas de Apoyo para la Decisión , Femenino , Edad Gestacional , Humanos , Lactante , Recién Nacido , Enfermedades Renales/etiología , Masculino , Oligohidramnios/diagnóstico por imagen , Embarazo , Pronóstico , Estudios Retrospectivos , Uretra/diagnóstico por imagen , Obstrucción Uretral/complicaciones , Obstrucción Uretral/diagnóstico por imagenRESUMEN
INTRODUCTION: The study aimed to evaluate the advantages of temporary inguinal ureterostomy in the management of neonates with uropathies and early or recurrent pyelonephritis. PATIENTS AND METHODS: We performed a retrospective analysis of all patients who underwent ureterostomies between 1989 and 2012, with specific regards to indications and outcomes. We also performed a survey of parents to evaluate their acceptance of diversion. RESULTS: We included 18 patients (12 primary high-grade vesicoureteral reflux [VUR] and 6 primary obstructive megaureters [MUs]). Indications were recurrent febrile urinary tract infections (UTIs) despite antibiotic prophylaxis, doubtful function of the overlying kidney for the oldest cases, when renal function was only assessed by intravenous urography, or both. Cutaneous diversion was performed between the ages of 2 weeks to 5 months (median: 1.8 months). Renal function was assessed prior to undiversion to choose between reimplantation and nephrectomy. The incidence of febrile UTIs significantly decreased during the period of diversion. Urinary diversion was judged socially acceptable by parents. Ureterostomy did not modify the overlying kidney function. CONCLUSION: Temporary inguinal ureterostomy does not enable better evaluation of renal function by suppressing the pressure of an obstacle or refluxing urines. Its remaining indication seems to be the prevention of recurrent UTIs in neonates and infants with VUR or MU, pending reimplantation.
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Obstrucción Ureteral/cirugía , Ureterostomía/métodos , Reflujo Vesicoureteral/cirugía , Antibacterianos/uso terapéutico , Niño , Preescolar , Humanos , Riñón/cirugía , Glomérulos Renales/patología , Masculino , Nefrectomía , Satisfacción del Paciente , Pielonefritis/cirugía , Recurrencia , Estudios Retrospectivos , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento , Derivación Urinaria , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/patología , Infecciones Urinarias/prevención & controlRESUMEN
KEY POINTS: L-type calcium channels in the CNS exist as two subunit forming channels, Cav1.2 and Cav1.3, which are involved in short- and long-term plasticity. We demonstrate that Cav1.3 but not Cav1.2 is essential for wind-up. These results identify Cav1.3 as a key conductance responsible for short-term sensitization in physiological pain transmission. We confirm the role of Cav1.2 in a model of long-term plasticity associated with neuropathic pain. Up-regulation of Cav1.2 and down-regultation of Cav1.3 in neuropathic pain underlies the switch from physiology to pathology. Finally, the results of the present study reveal that therapeutic targeting molecular pathways involved in wind-up may be not relevant in the treatment of neuropathy. ABSTRACT: Short-term central sensitization to pain temporarily increases the responsiveness of nociceptive pathways after peripheral injury. In dorsal horn neurons (DHNs), short-term sensitization can be monitored through the study of wind-up. Wind-up, a progressive increase in DHNs response following repetitive peripheral stimulations, depends on the post-synaptic L-type calcium channels. In the dorsal horn of the spinal cord, two L-type calcium channels are present, Cav1.2 and Cav1.3, each displaying specific kinetics and spatial distribution. In the present study, we used a mathematical model of DHNs in which we integrated the specific patterns of expression of each Cav subunits. This mathematical approach reveals that Cav1.3 is necessary for the onset of wind-up, whereas Cav1.2 is not and that synaptically triggered wind-up requires NMDA receptor activation. We then switched to a biological preparation in which we knocked down Cav subunits and confirmed the prominent role of Cav1.3 in both naive and spinal nerve ligation model of neuropathy (SNL). Interestingly, although a clear mechanical allodynia dependent on Cav1.2 expression was observed after SNL, the amplitude of wind-up was decreased. These results were confirmed with our model when adapting Cav1.3 conductance to the changes observed after SNL. Finally, our mathematical approach predicts that, although wind-up amplitude is decreased in SNL, plateau potentials are not altered, suggesting that plateau and wind-up are not fully equivalent. Wind-up and long-term hyperexcitability of DHNs are differentially controlled by Cav1.2 and Cav1.3, therefore confirming that short- and long-term sensitization are two different phenomena triggered by distinct mechanisms.
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Canales de Calcio Tipo L/metabolismo , Canales de Calcio/metabolismo , Neuralgia/metabolismo , Potenciales de Acción/fisiología , Animales , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatología , Masculino , Neuralgia/fisiopatología , Ratas , Ratas Wistar , Receptores de N-Metil-D-Aspartato/metabolismo , Médula Espinal/metabolismo , Médula Espinal/fisiopatología , Asta Dorsal de la Médula Espinal/metabolismo , Asta Dorsal de la Médula Espinal/fisiopatología , Nervios Espinales/metabolismo , Nervios Espinales/fisiopatología , Sinapsis/metabolismoRESUMEN
BACKGROUND: Numerous studies have focused on the association between endocrine-disrupting chemicals (EDCs) and hypospadias. Phenotype variability, the absence of representative comparison groups and concomitant genetic testing prevent any definitive conclusions. OBJECTIVE: To identify the role of occupational and environmental exposures to EDCs in nongenetic isolated hypospadias. DESIGN, SETTING, AND PARTICIPANTS: A total of 408 consecutive children with isolated hypospadias and 302 normal boys were prospectively included (2009-2014) in a multi-institutional study in the south of France, the area of the country with the highest prevalence of hypospadias surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: In patients without AR, SRD5A2, and MAMLD1 mutations, parental occupational and professional exposures to EDCs were evaluated based on European questionnaire QLK4-1999-01422 and a validated job-exposure matrix for EDCs. Environmental exposure was estimated using the zip code, the type of surrounding hazards, and distance from these hazards. Multivariate analysis was performed. RESULTS: Fetal exposure to EDCs around the window of genital differentiation was more frequent in the case of hypospadias (40.00% vs 17.55%, odds ratio 3.13, 95% confidence interval 2.11-4.65). The substances were paints/solvents/adhesives (16.0%), detergents (11.0%), pesticides (9.0%), cosmetics (5.6%), and industrial chemicals (4.0%). Jobs with exposure were more frequent in mothers of hypospadiac boys (19.73% vs 10.26%, p=0.0019), especially cleaners, hairdressers, beauticians, and laboratory workers. Paternal job exposure was more frequent in the cases of hypospadias (40.13% vs 27.48%, p=0.02). Industrial areas, incinerators, and waste areas were more frequent within a 3-km radius for mothers of hypospadiac boys (13.29% vs. 6.64%, p<0.00005). Association of occupational and environmental exposures increases this risk. CONCLUSIONS: This multicenter prospective controlled study with a homogeneous cohort of hypospadiac boys without genetic defects strongly suggests that EDCs are a risk factor for hypospadias through occupational and environmental exposure during fetal life. The association of various types of exposures may increase this risk. PATIENT SUMMARY: Our multi-institutional study showed that parental professional, occupational, and environmental exposures to chemical products increase the risk of hypospadias in children.