RESUMEN
BACKGROUND: The male genital examination is a common source of discomfort for the patient and medical provider. Performance of male genital examination is imperative; however, as many treatable diagnoses can be made. Undescended testicles (UDTs), hernias, testicular tumors, and urethral abnormalities are all potentially concerning findings which can be discovered on routine examination. OBJECTIVE: The objectives of this study are to determine the rate at which general pediatricians perform routine genitourinary (GU) examinations in the pediatric population and to determine the rate at which UDT are diagnosed or documented in the patient's history. The authors hypothesize the rate of pediatric GU examination during routine well-child visits to be in line with the previously reported rates in the adult literature. STUDY DESIGN: Nine hundred ninety-six consecutive male well-child visits conducted by general pediatricians at the study institution were reviewed. These visits were evaluated for documentation of a detailed GU examination as well as the presence of UDT from these examinations. In addition, past medical and surgical histories were reviewed to determine if a diagnosis of UDT was noted. RESULTS: Pediatricians at the study institution documented GU examinations 99.1% of the time during male well-child visits. Only 1.1% of the cohort had a documentation of UDT at any time point. Of the 11 patients with UDT, 6 boys (54.5%) had spontaneous descent with no referral to urology, whereas 5 (45.5%) required orchidopexy. DISCUSSION: Prior reports suggest 70-75% of routine office visits include a genital examination. None of these reports reviewed the pediatric population, thus making this review novel in this respect. In addition, the results are vastly different from these prior studies as the authors demonstrated over 99% of male well-child examinations included documentation of a thorough genital examination. A limitation of the study is its retrospective nature, which creates a lack of standardization across the data set. In addition, without being physically present in the examination room, one cannot discern whether an examination is simply being documented without actual performance because of the template format of the electronic medical record (EMR). Furthermore, the study was not designed to best evaluate the true rate of UDTs; therefore, the reported rate of 1.1% cannot be accurately associated with a particular age at diagnosis. CONCLUSIONS: Pediatricians do, in fact, document GU examinations on a routine basis. This finding cannot be taken with complete certainty as verification of actual examination performance is impractical. While the data demonstrated a lower than expected rate of UDT, depending upon age at diagnosis, this could indicate that although examinations are being documented, their accuracy may be diminished because of various factors at play in the healthcare system as a whole, including improper exam performance and EMR templates. Follow-up studies are required to verify these potentially changing rates of UDT and to determine if there is discordance between documentation and performance of GU examinations.
Asunto(s)
Actitud del Personal de Salud , Salud Infantil , Pediatras/estadística & datos numéricos , Examen Físico/estadística & datos numéricos , Sistema Urogenital/anatomía & histología , Adolescente , Niño , Preescolar , Estudios de Cohortes , Bases de Datos Factuales , Documentación/estadística & datos numéricos , Genitales Masculinos/anatomía & histología , Hospitales Pediátricos , Humanos , Incidencia , Lactante , Masculino , Evaluación de Resultado en la Atención de Salud , Examen Físico/métodos , Pautas de la Práctica en Medicina , Estudios Retrospectivos , Centros de Atención Terciaria , Estados UnidosRESUMEN
OBJECTIVE: Congenital lower urinary tract obstruction (LUTO) is a rare condition with high perinatal mortality and morbidity when associated with severe oligohydramnios or anhydramnios in the second trimester of pregnancy. Severe pulmonary hypoplasia and end-stage renal disease are the underlying causes of poor neonatal outcome in these cases. However, little is known about the subset of fetal LUTO that is associated with a normal volume of amniotic fluid at midgestation. The objective of the current study was to describe the natural history, underlying causes, survival and postnatal renal function outcomes in pregnancies with fetal LUTO and normal amniotic fluid volume during the second trimester of pregnancy. METHODS: This was a retrospective study of all pregnancies with fetal LUTO and normal amniotic fluid volume in the second trimester that received prenatal and postnatal care at our quaternary care institution between 2013 and 2017. Data on demographic characteristics, fetal interventions, perinatal survival, need for neonatal respiratory support, postnatal renal function and need for dialysis at the age of 1 and 24 months were analyzed. RESULTS: Of the 18 fetuses that met the study criteria, 17 (94.4%) survived the perinatal period. Eleven (61.1%) pregnancies developed oligohydramnios in the third trimester, six of which were eligible for and underwent fetal intervention with vesicoamniotic shunt placement, which was performed successfully in all six cases. Two (11.1%) neonates required respiratory support owing to pulmonary hypoplasia. At the age of 2 years, 14 children had follow-up information available, two (14.3%) of whom had normal renal function, eight (57.1%) had developed some degree of chronic kidney disease (Stage 1-4) and four (28.6%) had developed end-stage renal disease (ESRD), including two who had already manifested ESRD in the neonatal period. CONCLUSIONS: Most fetuses diagnosed prenatally with LUTO that is associated with a normal volume of amniotic fluid at midgestation will have a favorable outcome in terms of perinatal survival and few will need long-term respiratory support. However, these children are still at increased risk for chronic renal disease, ESRD and need for renal replacement therapy. Larger multicenter studies are needed to characterize the prenatal factors associated with postnatal renal function, and to investigate the role of fetal intervention in the group of fetuses that present with late-onset oligohydramnios and evidence of preserved fetal renal function. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Asunto(s)
Enfermedades Fetales/diagnóstico por imagen , Obstrucción Uretral/diagnóstico por imagen , Enfermedades Urológicas/diagnóstico por imagen , Adulto , Líquido Amniótico/diagnóstico por imagen , Preescolar , Femenino , Enfermedades Fetales/patología , Enfermedades Fetales/cirugía , Humanos , Lactante , Recién Nacido , Oligohidramnios/diagnóstico por imagen , Oligohidramnios/cirugía , Mortalidad Perinatal , Embarazo , Segundo Trimestre del Embarazo , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/etiología , Insuficiencia Renal Crónica/terapia , Estudios Retrospectivos , Medición de Riesgo , Ultrasonografía/métodos , Obstrucción Uretral/congénito , Obstrucción Uretral/mortalidad , Enfermedades Urológicas/congénitoRESUMEN
INTRODUCTION: Women are entering the subspecialty of pediatric urology at an accelerated rate. Gender differences affecting fellowship and job selection have been identified in other fields of medicine. OBJECTIVE: The objective of this study was to understand gender differences in pediatric urology fellowship and job selection and how they may affect the workforce. STUDY DESIGN: A 47-question electronic survey consisting of questions regarding demographics, residency training, and factors influencing fellowship and job selection was distributed to current fellows and recent graduates in pediatric urology in May 2017. RESULTS: A total of 111 recent and current fellows were contacted, and 72% completed the survey (55% female [F] and 45% male [M]; 61% current fellows and 39% recent fellows). Respondents rated factors important in choosing pediatric urology on a scale of 1-5 (1, not important and 5, extremely important), and the top three for both genders were 1-working with children, 2-influential mentors, and 3-bread and butter cases such as inguinal orchiopexy. During residency, 93% of respondents reported having influential mentors in pediatric urology. However, mentorship was more important in fellowship choice for males than females (3.6 F, 4.1 M; P-value = 0.048), and 45% reported having only male mentors. Rating factors important in job choice on a scale of 1-5, respondents reported the top factors as 1-rapport with partners/mentorship (4.5), 2-geography/family preferences (4.3), and 3-participation in mentoring/teaching (3.8). Although most job selection criteria were rated similarly between genders, females rated call schedule higher than males (3.5 F, 2.9 M, P-value = 0.009). Although most females and males (79% of F, 78% of M, P-value = 0.868) sought primarily academic positions, a smaller proportion of females accepted academic positions (52% of F, 72% of M, P-value 0.26), and females reported lower satisfaction regarding the availability of jobs on a scale of 1-5 (1, very dissatisfied and 5, very satisfied; 3.1 F, 3.7 M; P-value = 0.034), particularly in academic positions (3.1 F, 3.7 M; P-value = 0.06). This difference was more pronounced in current fellows than recent graduates and may represent a worsening trend. CONCLUSION: Although significant gender differences in fellowship and job selection may exist in other fields, we found that women and men choose pediatric urology fellowships and jobs using similar criteria, which include work-life balance. Gender differences exist in the influence of mentors, indicating a need for more female mentors. While men and women sought similar types of jobs, women were less satisfied with the availability of jobs, particularly academic jobs, than men, which warrants further investigation.
Asunto(s)
Becas/estadística & datos numéricos , Pediatría/estadística & datos numéricos , Médicos Mujeres/estadística & datos numéricos , Urología/estadística & datos numéricos , Selección de Profesión , Femenino , Humanos , Masculino , Mentores/estadística & datos numéricos , Autoinforme , Distribución por SexoRESUMEN
BACKGROUND: Hypospadias is a common genitourinary malformation and there are conflicting data on whether its prevalence is increasing. Previous studies have described associations with risk factors including small for gestational age (SGA), multiple gestation birth, environmental influences, and maternal factors. OBJECTIVE: The objective of this study was to examine birth prevalence of hypospadias and hypospadias risk factors in a large national dataset and to evaluate for changes from 1997 to 2012. We hypothesized that any increase in the birth prevalence of hypospadias would be associated with an increase in risk factors such as SGA, prematurity, or multiple gestation birth. STUDY DESIGN: The Kids' Inpatient Database was used to generate national estimates for prevalence of males born with hypospadias, SGA, prematurity, or to a multiple gestation and then prevalences were evaluated for association with time. Multivariable logistic regression was used to evaluate whether birth prevalence of hypospadias was associated with increasing year, SGA, prematurity, and multiple gestation birth. RESULTS: The estimated birth prevalence of hypospadias increased from 6.1 per 1000 births (95% confidence interval [CI] 5.9 to 6.3) to 6.8 per 1000 births (95% CI 6.7 to 7.0), an 11.5% increase from 1997-2012 (P = 0.014). Among male births, the prevalence of SGA increased 74%, multiple gestation increased 25%, and prematurity increased 20% (P < 0.001 for all) (Summary Figure). A risk factor was seen in around 20% of males born with hypospadias. Hypospadias birth prevalence also increased in males without risk factors but was not statistically significant (9.1% increase, P = 0.5). On multivariable logistic regression, being born SGA (odds ratio [OR] = 3.3), to a multiple gestation (OR = 1.1), or premature (OR 1.9) were associated with increased odds of hypospadias (P < 0.01 for all), whereas increasing year was not (P = 0.3). CONCLUSIONS: The estimated birth prevalence of hypospadias in the United States increased from 6.1 to 6.8 per 1000 births from 1997 to 2012. Known hypospadias risk factors of SGA birth, multiple gestation birth, and premature birth also increased over this time to a higher degree. About 20% of males born with hypospadias had one of these risk factors. The birth prevalence of hypospadias in males without any studied risk factors also increased, but this was not statistically significant. More studies are needed to evaluate whether this increase in hypospadias prevalence is due to increases in known hypospadias risk factors, new environmental exposures, improved diagnosis at birth, some combination, or unrelated causes.
Asunto(s)
Hipospadias/epidemiología , Humanos , Recién Nacido , Masculino , Prevalencia , Factores de Riesgo , Factores de Tiempo , Estados Unidos/epidemiologíaRESUMEN
INTRODUCTION: Non-refluxing ureteral reimplantation is favored in pediatric renal transplantation to prevent complications, such as vesicoureteral reflux (VUR) in the transplant ureter. VUR resulting in febrile urinary tract infections remains a problem in this population, leading to repeated hospitalizations and increased morbidity. Revision of the vesicoureteral anastomosis can be a surgical challenge due to scar tissue and tenuous vascularity of the transplant ureter. Therefore, alternative options such as endoscopic injection of Deflux at the neo-orifice and surveillance with prophylactic antibiotics have emerged as potential treatment modalities for transplant ureter VUR. OBJECTIVE: The authors reviewed their experience of the management of VUR in the transplant ureter, comparing outcomes of various modalities. STUDY DESIGN: With Institutional Review Board approval, a retrospective chart review of all renal transplant patients from January 2002 to January 2017 was conducted. All patients with VUR on voiding cystourethrogram (VCUG) after surgery were identified. Indications for end-stage renal disease, urologic comorbidities, pretransplant VCUG, and operative details were recorded. After transplantation, febrile urinary tract infections, ultrasound findings, and any further interventions-surveillance, subureteral endoscopic injection of Deflux, or ureteral reimplantation-were documented along with their outcomes. RESULTS: Overall, VUR was identified in 35/285 (12.3%) transplant patients after a non-refluxing ureteroneocystostomy. VUR was managed with surveillance in 17/35 (49%), intravesical Deflux injection in 11/35 (31%), and immediate redo ureteral reimplantation in 7/35 (20%). Ten out of 11 patients undergoing Deflux injection had a postoperative VCUG. All patients developed VUR recurrence; the majority showed immediate failure and only 1/10 showed late recurrence. Of the immediate failures, 3/9 patients were maintained on prophylactic antibiotics, and 6/9 patients underwent ureteral reimplantation. In these six patients undergoing reimplantation after failed Deflux, 3/6 (50%) patients required additional surgeries: One patient developed recurrence of reflux and two patients developed ureterovesical junction obstruction. In contrast, no complications were seen in patients undergoing primary ureteral reimplantation. DISCUSSION: The study is limited by low numbers and a retrospective design. However, the results of this study differ significantly from the published Deflux series showing a success rate of more than 50% in the treatment of transplant kidney VUR. In fact, post-Deflux redo ureteral reimplantation was associated with an increased risk of postoperative complication. CONCLUSION: The use of Deflux in the post-transplant setting has poor results. In the study series, 11/11 patients demonstrated clinical and radiographic failure. Therefore, as an institution the authors do not recommend Deflux as first-line treatment of VUR in the transplant patient.
Asunto(s)
Trasplante de Riñón , Complicaciones Posoperatorias/terapia , Reflujo Vesicoureteral/terapia , Niño , Dextranos/uso terapéutico , Femenino , Humanos , Ácido Hialurónico/uso terapéutico , Masculino , Prótesis e Implantes , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
INTRODUCTION: Some children who sustain high-grade blunt renal injury may require operative intervention. In the present study, it was hypothesized that there are computed tomography (CT) characteristics that can identify which of these children are most likely to need operative intervention. MATERIALS AND METHODS: A retrospective review was performed of all pediatric blunt renal trauma patients at a single level-I trauma center from 1990 to 2015. Inclusion criteria were: children with American Association for the Surgery of Trauma (AAST) Grade-IV or V renal injuries, aged ≤18 years, and having available CT images with delayed cuts. The CTs were regraded according to the revised AAST grading system proposed by Buckley and McAninch in 2011. Radiographic characteristics of renal injury were correlated with the primary outcome of any operative intervention: ureteral stent, angiography, nephrectomy/renorrhaphy, and percutaneous nephrostomy/drain. RESULTS: One patient had a Grade-V injury and 26 patients had Grade-IV injuries. Nine patients (33.3%) underwent operative interventions. Patients in the operative intervention cohort were more likely to manifest a collecting system filling defect (P = 0.040) (Fig. A) and lacked ureteral opacification (P = 0.010). The CT characteristics, including percentage of devascularized parenchyma, medial contrast extravasation, intravascular contrast extravasation, perirenal hematoma distance and laceration location, were not statistically significant. Of the 21 patients who had a collecting system injury, eight (38.1%) needed ureteral stents. Renorrhaphy was necessary for one patient. Although the first operative intervention occurred at a median of hospital day 1 (range 0.5-2.5), additional operative interventions occurred from day 4-16. Thus, it is prudent to closely follow-up these patients for the first month after injury. Two patients with complex renal injuries had an accessory renal artery resulting in well-perfused upper and lower pole fragments, and were managed nonoperatively without readmission (Fig. B). CONCLUSIONS: Collecting system defects and lack of ureteral opacification were significantly associated with failure of nonoperative management. A multicenter trial is needed to confirm these findings and whether nonsignificant CT findings are associated with operative intervention. In the month after renal injury, these patients should be mindful of any changes in symptoms, and maintain a low index of suspicion for an emergency room visit. For the physician, close follow-up and appropriate counseling of these high-risk patients is advised.
Asunto(s)
Riñón/diagnóstico por imagen , Riñón/lesiones , Tomografía Computarizada por Rayos X , Heridas no Penetrantes/diagnóstico por imagen , Heridas no Penetrantes/terapia , Adolescente , Niño , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Estudios Retrospectivos , Insuficiencia del TratamientoRESUMEN
OBJECTIVE: To present a single center experience of a standardized prenatal multidisciplinary management protocol for fetal lower urinary tract obstruction (LUTO) and to propose a classification of fetal LUTO based on disease severity. METHODS: This was a retrospective cohort study of 25 consecutive fetal patients with prenatal diagnosis of primary LUTO. Fetal intervention was offered after evaluation by a multidisciplinary team. Analyses were conducted using Bayesian methodology to determine predictors of survival at 6 months postpartum. Odds ratios (ORs) with 95% credibility intervals are reported. RESULTS: Fifteen (60.0%) of the 25 patients referred for assessment survived to postnatal evaluation. Fetal vesicoamniotic shunt was placed in 14 (56.0%) patients with 12 survivors. Multivariable analysis suggested that fetal intervention (OR, 6.97 (0.88-70.16), Pr(OR > 1) = 96.7%), anhydramnios (OR, 0.12 (0.04-0.35), Pr(OR < 1) = 99.9%), favorable fetal urine analysis (OR, 3.98 (0.63-25.15), Pr(OR > 1) = 92.7%) and absence of renal cortical cysts (OR, 3.9 (0.66-24.2), Pr(OR > 1) = 93.3%) were predictors of survival. CONCLUSIONS: Fetal intervention and fetal renal function were independently associated with postnatal survival of fetuses with LUTO. A classification based on the severity of disease is proposed. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
Asunto(s)
Cistoscopía/métodos , Enfermedades Fetales/cirugía , Atención Prenatal/métodos , Obstrucción del Cuello de la Vejiga Urinaria/cirugía , Teorema de Bayes , Manejo de la Enfermedad , Femenino , Enfermedades Fetales/diagnóstico , Humanos , Pruebas de Función Renal , Embarazo , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Obstrucción del Cuello de la Vejiga Urinaria/diagnósticoRESUMEN
OBJECTIVE: To describe the surgical technical aspects associated with the development of urological fistulas after fetal antegrade cystoscopic laser fulguration of the posterior urethral valves (PUV). METHODS: The perioperative data for all fetal cystoscopies performed between January 2004 and August 2013 at three institutions in the USA, France and Brazil were reviewed, with particular emphasis on surgical technical aspects of the procedure and the complications encountered. RESULTS: A total of 40 fetal cystoscopies were performed at the three institutions. Laser fulguration of the PUV was performed in 23 of these cases, with a survival rate of 60.9% (14/23) and normal renal function in 85.7% (12/14) of these infants. Urological fistulas were diagnosed postnatally in four (10%) newborns. The presence of fistulas was associated with a higher gestational age at diagnosis of PUV (P < 0.01) and with the use of semi-curved rather than curved sheaths (P < 0.01), the use of a diode laser (P < 0.01) and the use of higher laser power and energy (P < 0.01 and P < 0.01, respectively), as well as with less operator experience (P < 0.01) and with absence of fetal anesthesia/immobilization (P = 0.02). CONCLUSION: Urological fistulas are a severe complication of fetal cystoscopic laser fulguration of PUV and are associated with type, energy and power settings of the laser and instrumentation. The use of appropriate technique and proper training of the operator are necessary to perform this fetal intervention safely.
Asunto(s)
Electrocoagulación/efectos adversos , Terapia por Láser/efectos adversos , Complicaciones Posoperatorias/etiología , Uretra/cirugía , Obstrucción Uretral/cirugía , Fístula Urinaria/etiología , Brasil , Cistoscopía , Electrocoagulación/métodos , Francia , Humanos , Recién Nacido , Terapia por Láser/métodos , Masculino , Factores de Riesgo , Resultado del Tratamiento , Estados UnidosRESUMEN
The safety of robenacoxib, a nonsteroidal anti-inflammatory drug with high selectivity for inhibition of the cyclooxygenase (COX)-2 isoform of COX, was investigated in the cat in two randomized, blinded, placebo-controlled, parallel-group studies. Robenacoxib was administered orally to healthy young domestic short-hair cats at dosages of 0 (placebo), 5 and 10 mg/kg once daily for 28 days (study 1) and at 0 (placebo), 2, 6 and 10 mg/kg twice daily for 42 days (study 2). The recommended minimum dosage for robenacoxib tablets in cats is 1 mg/kg once daily (range 1-2.4 mg/kg). Relative to placebo treatment, no toxicologically significant effects of robenacoxib were recorded in either study, based on general observations of health, haematological and clinical chemistry variables and urinalyses in life, and by post mortem organ weight, gross pathology and histopathology assessments. Pharmacokinetic-pharmacodynamic simulations indicated that all dosages of robenacoxib were associated with marked inhibition of COX-2 at peak effect (median I(max) 97.8-99.4% inhibition) with lesser inhibition of COX-1 (median I(max) 26.8-58.3% inhibition). Inhibition of the COXs was short lasting, with >10% median inhibition persisting for 4.0 h for COX-2 and 1.5 h for COX-1. These levels of inhibition of COX-1 and COX-2 twice daily with robenacoxib were not associated with any detectable toxicity, suggesting that, as previously described in dogs, the high safety index of robenacoxib in cats may be related to a combination of its high COX-2 selectivity and short residence time in the central compartment.
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Difenilamina/análogos & derivados , Fenilacetatos/efectos adversos , Administración Oral , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/sangre , Gatos , Inhibidores de la Ciclooxigenasa 2/administración & dosificación , Inhibidores de la Ciclooxigenasa 2/efectos adversos , Inhibidores de la Ciclooxigenasa/administración & dosificación , Inhibidores de la Ciclooxigenasa/efectos adversos , Difenilamina/administración & dosificación , Difenilamina/efectos adversos , Difenilamina/sangre , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Fenilacetatos/administración & dosificación , Fenilacetatos/sangreRESUMEN
AIM: To demonstrate the safety in weaned lambs of repetitive oral doses of monepantel, an amino-acetonitrile derivative (AAD), when administered at the proposed maximum recommended dose (MRD) and three and five times the MRD over 24 weeks. METHODS: A randomised controlled blinded study design was used. Fifty-six weaned lambs were randomly allocated into a control group, the MRD (3.75 mg/kg) and three (11.25 mg/ kg) and five (18.75 mg/kg) times the MRD treatment groups (n=7 castrated males plus seven females each). Treatment doses of monepantel were calculated based on the MRD of 3.75 mg/ kg, and administered orally on eight occasions at intervals of approximately 21 days. Detailed recording at multiple time points were made of veterinary examinations, observations for adverse events, bodyweight measurements, faecal scores, and haematology, clinical chemistry and coagulation variables. Gross pathology (including measurement of organ weights) and histopathology were performed at the completion of the study. RESULTS: All lambs treated with monepantel and those in the control group thrived, grew and behaved normally to the end of the study. No treatment-related, toxicologically relevant adverse events, clinical observations or macroscopic or microscopic changes were observed. Furthermore, there were no significant differences in bodyweight or organ weights, and haematological, clinical chemistry or coagulation variables between lambs treated with monepantel and control lambs. CONCLUSIONS AND CLINICAL RELEVANCE: Repeated oral administration of monepantel at the MRD and three and five times the MRD every 3 weeks for eight treatments was not associated with any treatment-related adverse effects and was systemically very well tolerated in weaned, growing lambs. This study demonstrated that this population of lambs could tolerate accidental overdoses of up to five times the MRD of monepantel or prolonged repetitive administration at recommended doses or overdoses.
Asunto(s)
Aminoacetonitrilo/análogos & derivados , Antihelmínticos/efectos adversos , Antihelmínticos/uso terapéutico , Enfermedades de las Ovejas/tratamiento farmacológico , Administración Oral , Aminoacetonitrilo/efectos adversos , Aminoacetonitrilo/uso terapéutico , Animales , Animales Recién Nacidos , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Distribución Aleatoria , Seguridad , Ovinos , Resultado del TratamientoRESUMEN
The evaluation of potential adverse effects of pharmaceuticals on the immune system is part of the standard drug development procedures and needs to be available prior to the start of phase III clinical trials. Although the histopathological assessment of lymphoid organs/tissues is considered fundamental for the identification and characterization of immunotoxic reactions, additional investigations are now recommended by the European guidelines for repeated-dose toxicity testing of medicinal products in order to achieve an accurate assessment of immune system functionality with regard to immunomodulation. In the present paper, we describe and discuss a study design which permits the investigation of the immune function in a 4-week study in rats following immunization by subcutaneous administration of the T-dependent antigen Keyhole Limpet Hemocynin (KLH). This includes assessment of hematology parameters, titration of KLH-specific antibodies in serum, lymphocyte immunophenotyping in blood, thymus, spleen and lymph nodes, macroscopic pathology and histopathological evaluation of the lymphatic organs/tissues and of the injection sites.
Asunto(s)
Adyuvantes Inmunológicos/toxicidad , Antígenos/toxicidad , Hemocianinas/toxicidad , Tejido Linfoide/efectos de los fármacos , Pruebas de Toxicidad/métodos , Animales , Formación de Anticuerpos/efectos de los fármacos , Recuento de Células , Relación Dosis-Respuesta Inmunológica , Femenino , Inmunofenotipificación , Inyecciones Subcutáneas , Tejido Linfoide/patología , Masculino , Ratas , Proyectos de Investigación , Piel/efectos de los fármacos , Piel/patología , Linfocitos T/efectos de los fármacos , Linfocitos T/patologíaRESUMEN
We report experimental measurements of neutron production from collisions of neutron beams with polyethylene blocks simulating tissue at the Los Alamos National Laboratory Neutron Science Center and 1 GeV/amu iron nuclei with spacecraft shielding materials at the Brookhaven National Laboratory AGS.
Asunto(s)
Interacciones de Partículas Elementales , Neutrones , Polietileno/efectos de la radiación , Protección Radiológica , Nave Espacial , Humanos , Hierro , Modelos Anatómicos , Dosis de Radiación , Radiometría , Medición de RiesgoRESUMEN
PURPOSE: In patients suspected to have the vertebral, anal, tracheoesophageal, renal, radial, cardiac and limb abnormalities (VACTERL) association we studied the frequency of upper urinary tract anomalies, prevalence of these features, predictability of upper tract pathology and proper screening evaluation. MATERIALS AND METHODS: From 1991 to 1998 we identified 55 patients with the VACTERL association. Upper urinary tract assessment, including initial renal ultrasound and voiding cystourethrography, and followup data were available for 29 boys and 15 girls. Patients were considered to have the VACTERL association when 3 or more organ systems were involved. RESULTS: Average followup was 5.4 years. Upper urinary tract involvement was noted in 41 of the 44 patients (93.2%) and vesicoureteral reflux in 17 (25 renal units). Of the kidneys 21 were hydronephrotic without reflux or obstruction, 10 were solitary, 3 were multicystic dysplastic, 8 were obstructed and only 17 were normal. A total of 27 patients (61%) underwent at least 1 genitourinary procedure, primarily ureteroneocystotomy. All children were alive at the last followup. CONCLUSIONS: The VACTERL association involves multiple serious anomalies. However, these infants generally have a good outcome. Since the upper urinary system is the most common organ system involved, patients should receive prophylactic antibiotics until an initial urological assessment with renal ultrasound and voiding cystourethrography is performed. It is essential for physicians to know that most children with the VACTERL association have urological involvement that requires treatment and long-term management.
Asunto(s)
Anomalías Múltiples , Anomalías Urogenitales , Niño , Femenino , Humanos , Hidronefrosis/etiología , Riñón/anomalías , Masculino , Estudios Retrospectivos , Reflujo Vesicoureteral/etiologíaRESUMEN
This paper describes a modification of bilateral posterior iliac osteotomies for bladder exstrophy, in which a strip of ilium is resected subperiosteally lateral to the sacroiliac joints, allowing easier anterior closure with less breakdown compared with traditional osteotomies. Thirty-one children underwent repair of bladder exstrophy between 1974 and 1994. Orthopaedic procedures included: closed reduction and cast application in the newborn period (four patients), classic bilateral posterior iliac osteotomies (12 patients), and bilateral posterior resection osteotomies (15 patients). Dehiscence occurred after one closed reduction, five classic osteotomies, and one resection osteotomy. Urinary continence was obtained in four patients who underwent closed reduction, nine patients who underwent classic posterior osteotomies, and nine patients who underwent posterior resection osteotomies.
Asunto(s)
Extrofia de la Vejiga/cirugía , Ilion/cirugía , Osteotomía/métodos , Extrofia de la Vejiga/complicaciones , Extrofia de la Vejiga/diagnóstico por imagen , Moldes Quirúrgicos , Preescolar , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Osteotomía/efectos adversos , Osteotomía/instrumentación , Radiografía , Recurrencia , Resultado del Tratamiento , Incontinencia Urinaria/etiologíaRESUMEN
PURPOSE: Cryptorchidism is the most common congenital abnormality of the genitalia. However, its exact etiology remains to be defined. Homeobox (HOX) containing genes have a key role in the morphogenesis of segmental structures along the primary body axis, including the urogenital mesenchyma. In male mice with a targeted deletion of the HOXA10 gene cryptorchidism manifests in the absence of other major defects. Because to our knowledge this gene has never been examined for alterations in humans, we evaluated whether mutations of HOXA10 are associated with cryptorchidism in humans. MATERIALS AND METHODS: Genomic deoxyribonucleic acid (DNA) was extracted from human blood or tissue samples from 16 noncryptorchid control subjects and 45 cryptorchid boys. To screen for mutations exons 1 and 2 of the HOXA10 gene were amplified individually by polymerase chain reaction using 6 overlapping oligonucleotide primer pairs. Single strand conformational polymorphism (SSCP) analysis of the amplified radiolabeled DNA fragments was performed. Variant band shifts were detected due to abnormal migration of the denatured DNA fragment compared to controls, suggesting an alteration in the DNA sequence. Sequence analysis of these variant bands was then done to define any mutations. RESULTS: SSCP analysis revealed variants in 2 controls. Of the 45 samples from cryptorchid patients 30 had SSCP variants in exon 1. No variants were found in other regions of the gene. Sequence analysis revealed several DNA polymorphisms in exon 1 in controls and boys with cryptorchidism. Other nucleotide changes (point mutations) were noted only in exon 1 in the DNA of 5 cryptorchid patients, of whom 1 had a 24 nucleotide deletion. CONCLUSIONS: Our initial analysis of the HOXA10 gene in humans demonstrates that genetic alterations of this gene may be present in some boys with cryptorchidism. HOXA10 polymorphisms exist in normal control subjects as well as in cryptorchid patients. Further analysis of the function of the mutated protein will elucidate the role of this gene as a potential causative factor of testicular descent.
Asunto(s)
Criptorquidismo/genética , Genes Homeobox/genética , Mutación , Niño , ADN de Neoplasias/análisis , Humanos , Masculino , Análisis de Secuencia de ADNRESUMEN
PURPOSE: We explored the psychological adjustment of children with bladder or cloacal exstrophy. MATERIALS AND METHODS: We assessed 29 subjects with a mean age plus or minus standard deviation of 7.8 +/- 3.97 years using age appropriate standard psychological instruments. Psychological adjustment scores in the exstrophy group were compared to the norms of the various instruments. Subjects were divided into dichotomous groups according to several medical and demographic factors. For each factor the differences between the means of the 2 groups on the outcome variables were calculated using a t test. RESULTS: Children with exstrophy perceived their appearance more positively than the norm. Older children performed more poorly than younger children in adaptive behavior, specifically in skills related to functioning in school. Children who achieved continence after age 4 years were more likely to have problems with acting out behavior. There were no differences in adjustment in boys versus girls, bladder versus cloacal exstrophy, type of continence strategy or gender reassignment versus no reassignment. CONCLUSIONS: Children with exstrophy did not have clinical psychopathology. Differences existed in adaptive and acting out behavior rather than depression or anxiety, suggesting that improved outcomes may be achieved through a focus on normal adaptation rather than on potential psychological distress.
Asunto(s)
Adaptación Psicológica , Extrofia de la Vejiga/psicología , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Factores de TiempoRESUMEN
PURPOSE: Multiple theories of testicular descent exist but there is no consensus. Cryptorchidism is a component of the androgen insensitivity syndrome, suggesting that testicular descent may be at least partially under the control of androgenic stimulation. To determine whether isolated cryptorchidism may be caused by androgen insensitivity, we screened a population of boys with isolated cryptorchidism for the presence of androgen receptor gene alterations. MATERIALS AND METHODS: Deoxyribonucleic acid (DNA) was isolated from tissue collected from 21 patients with isolated cryptorchidism during orchiopexy. Patient selection was biased to maximize the likelihood of detection of a genetic etiology of cryptorchidism. The DNA was screened for androgen receptor gene alterations in exons 2 to 8 using single strand conformational polymorphism analysis. RESULTS: No abnormalities in the androgen receptor gene were detected by single strand conformational polymorphism analysis in any patient. CONCLUSIONS: Mutations of the androgen receptor gene in the hormone and DNA binding domains of the protein appear to be an unlikely cause of isolated cryptorchidism.
Asunto(s)
Aberraciones Cromosómicas/genética , Criptorquidismo/genética , Receptores Androgénicos/genética , Niño , Trastornos de los Cromosomas , ADN/análisis , Humanos , MasculinoRESUMEN
PURPOSE: Dismembered pyeloplasty for the correction of ureteropelvic junction obstruction can be performed through a flank or dorsal lumbar incision. We compared the records of children who had undergone pyeloplasty by each approach to determine if 1 technique was more advantageous. MATERIALS AND METHODS: We retrospectively reviewed the records of 33 consecutive children undergoing simple dismembered pyeloplasty by a single pediatric urologist from 1992 to 1996. The flank approach was used exclusively in the first group of patients who underwent repair in 1992 to 1993 and the dorsal lumbar incision was used exclusively in the second group after 1993. Data were obtained from hospital and clinic records, and both groups were compared with the 2-tailed t test. RESULTS: Pyeloplasty was done by dorsal lumbar incision in 16 cases and via the flank approach in 17. One patient in each group had undergone simultaneous bilateral pyeloplasties. Although overall comparison of both groups revealed no differences in operative time, in children older than 1 year pyeloplasty through a dorsal lumbar incision (108.5 minutes) was statistically significantly faster than the flank approach (144.4 minutes). Hospital stay was approximately 2 days shorter in infants who had a dorsal lumbar (25.7 hours) versus a flank incision (73 hours), and this difference did reach statistical significance if the bilateral pyeloplasty patients were excluded. Hospital costs were less for the dorsal lumbar group but the difference was not statistically significant. Success and complication rates were similar between groups with 2 patients in each group requiring additional procedures. Review of other series of repair of ureteropelvic junction obstruction demonstrated that the dorsal lumbar repair had equivalent or shorter operative times and lengths of hospitalization compared to newer endoscopic methods, and the outcomes were superior. CONCLUSIONS: The dorsal lumbar incision is a safe and efficacious approach to pyeloplasty and may be more cost-effective. In our series it was significantly faster in patients older than 1 year and resulted in shorter hospital stays in those younger than 1 year old.
Asunto(s)
Pelvis Renal/cirugía , Obstrucción Ureteral/cirugía , Niño , Preescolar , Costo de Enfermedad , Precios de Hospital , Humanos , Lactante , Recién Nacido , Tiempo de Internación , Estudios Retrospectivos , Resultado del Tratamiento , Obstrucción Ureteral/economíaRESUMEN
PURPOSE: Transverse island flaps of inner preputial skin have provided a reliable technique for the repair of proximal hypospadias. The flap may be used to create a neourethra by tubularizing the flap after urethral transection or applying the flap as an onlay patch onto an intact urethral plate. We retrospectively analyzed our experience with these 2 techniques to compare outcomes. MATERIALS AND METHODS: During 11 years 132 patients underwent hypospadias repair by a single surgeon using an onlay (58) or tubularized (74) island flap technique. Surgical results were reviewed retrospectively. RESULTS: At a mean followup of 20.3 months the overall complication rate was 36% for tubularized and 31% for onlay repair, and fistula rates were 14 and 17%, respectively. Despite similar fistula rates tubularized repairs tended to have larger fistulas that required more complex repair (p = 0.0147). In 9 patients who underwent tubularize repair diverticula developed, whereas no diverticula developed after onlay repair (p = 0.0162). The rates of urethral stricture, wound infection, residual chordee and cosmetic complications were not statistically significantly different between repairs. The use of double faced repair in 30 patients provided no difference in outcome in comparison to the overall study cohort. CONCLUSIONS: Hypospadias repair using transverse island flaps offers reliable and durable outcomes. While overall complication rates were not greatly different between tubularized and onlay flap repairs, onlay repair tended to result in fistulas of smaller size and diverticula did not develop.