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1.
Nat Biomed Eng ; 5(12): 1407-1408, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34897287
2.
Genet Med ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34906515

RESUMO

PURPOSE: Congenital anomalies of the kidneys and urinary tract (CAKUT) constitute the leading cause of chronic kidney disease in children. In total, 174 monogenic causes of isolated or syndromic CAKUT are known. However, syndromic features may be overlooked when the initial clinical diagnosis of CAKUT is made. We hypothesized that the yield of a molecular genetic diagnosis by exome sequencing (ES) can be increased by applying reverse phenotyping, by re-examining the case for signs/symptoms of the suspected clinical syndrome that results from the genetic variant detected by ES. METHODS: We conducted ES in an international cohort of 731 unrelated families with CAKUT. We evaluated ES data for variants in 174 genes, in which variants are known to cause isolated or syndromic CAKUT. In cases in which ES suggested a previously unreported syndromic phenotype, we conducted reverse phenotyping. RESULTS: In 83 of 731 (11.4%) families, we detected a likely CAKUT-causing genetic variant consistent with an isolated or syndromic CAKUT phenotype. In 19 of these 83 families (22.9%), reverse phenotyping yielded syndromic clinical findings, thereby strengthening the genotype-phenotype correlation. CONCLUSION: We conclude that employing reverse phenotyping in the evaluation of syndromic CAKUT genes by ES provides an important tool to facilitate molecular genetic diagnostics in CAKUT.

3.
Am J Med Genet A ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34525250

RESUMO

Congenital anomalies of the kidneys and urinary tract (CAKUT) constitute the most common cause of early-onset chronic kidney disease. In a previous study, we identified a heterozygous truncating variant in nuclear receptor-interacting protein 1 (NRIP1) as CAKUT causing via dysregulation of retinoic acid signaling. This large family remains the only family with NRIP1 variant reported so far. Here, we describe one additional CAKUT family with a truncating variant in NRIP1. By whole-exome sequencing, we identified one heterozygous frameshift variant (p.Asn676Lysfs*27) in an isolated CAKUT patient with bilateral hydroureteronephrosis and right grade V vesicoureteral reflux (VUR) and in the affected father with left renal hypoplasia. The variant is present twice in a heterozygous state in the gnomAD database of 125,000 control individuals. We report the second CAKUT family with a truncating variant in NRIP1, confirming that loss-of-function mutations in NRIP1 are a novel monogenic cause of human autosomal dominant CAKUT.

4.
Neurourol Urodyn ; 40(8): 1981-1988, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34486166

RESUMO

AIMS: We aimed to describe the effectiveness of Onabotulinumtoxin A (Botox) in children with neurogenic bladder (NGB) unresponsive to medical therapy to determine urodynamic parameters predictive of success. METHODS: Children receiving Botox for refractory NGB, between 2008 and 2019, from a single academic center, were included in this study. Botox success was defined as improvement of incontinence and/or urodynamic parameters. RESULTS: Of 34 patients who received Botox, 13 (38.2%) had a positive response from their first injection, with improvement in capacity by a median of 35% of expected capacity for age compared to only a 9% increase in those who did not respond clinically. When patients were divided into groups by baseline urodynamic parameters, high-pressure (Pdetmax > 20 cm H2 O) patients had significantly greater improvement in compliance compared with low-pressure patients (p = 0.017). Low compliance patients (<10 ml/cm H2 O) had a dramatic improvement of 3.08 ml/cm H2 O in their compliance compared with minimal change in the high compliance group (p = 0.003). Finally, low-capacity (<50% of expected CC) patients had significant improvement in capacity and compliance when compared with high-capacity patients (p = 0.004 and p = 0.036, respectively). Improvement in detrusor overactivity (DO) was noted in both the clinical responders and non-responders. CONCLUSION: In our series, 38% had clinical success with intradetrusor Botox injections for refractory neurogenic bladder. When successful, improvement in capacity and compliance, DO, and/or incontinence was consistent with prior literature. While we could not determine which parameters predicted success, subdividing patients into categories based on baseline urodynamic parameters identified who would benefit from Botox treatment based on differential improvements in capacity and compliance. At least 1 injection of Botox should be considered for a subset of children with refractory NGB, before undertaking more invasive treatments.


Assuntos
Toxinas Botulínicas Tipo A , Fármacos Neuromusculares , Bexiga Urinaria Neurogênica , Bexiga Urinária Hiperativa , Toxinas Botulínicas Tipo A/uso terapêutico , Criança , Humanos , Fármacos Neuromusculares/uso terapêutico , Bexiga Urinaria Neurogênica/tratamento farmacológico , Bexiga Urinária Hiperativa/tratamento farmacológico , Urodinâmica
5.
Artigo em Inglês | MEDLINE | ID: mdl-34473308

RESUMO

BACKGROUND: Congenital anomalies of the kidneys and urinary tract (CAKUT) constitute the most common cause of chronic kidney disease in the first three decades of life. Variants in four Forkhead box (FOX) transcription factors have been associated with CAKUT. We hypothesized that other FOX genes, if highly expressed in developing kidney, may also represent monogenic causes of CAKUT. METHODS: We here performed whole exome sequencing (WES) in 541 families with CAKUT and generated 4 lists of CAKUT candidate genes: A) 36 FOX genes showing high expression during renal development, B) 4 FOX genes known to cause CAKUT to validate list A; C) 80 genes that we identified as unique potential novel CAKUT candidate genes when performing WES in 541 CAKUT families, and D) 175 genes identified from WES as multiple potential novel CAKUT candidate genes. RESULTS: To prioritize potential novel CAKUT candidates in FOX gene family, we overlapped 36 FOX genes (list A) with list C and D of WES-derived CAKUT candidates. Intersection with list C, identified a de novo FOXL2 in-frame deletion in a patient with eyelid abnormalities and ureteropelvic junction obstruction, and a homozygous FOXA2 missense variant in a patient with horseshoe kidney. Intersection with list D, identified a heterozygous FOXA3 missense variant in a CAKUT family with multiple affected individuals. CONCLUSION: We hereby identified FOXL2, FOXA2 and FOXA3 as novel monogenic candidate genes of CAKUT, supporting the utility of a paralog-based approach to discover mutated genes associated with human disease.

6.
Nat Biomed Eng ; 5(10): 1115-1130, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34155355

RESUMO

Silicone is widely used in chronic implants and is generally perceived to be safe. However, textured breast implants have been associated with immune-related complications, including malignancies. Here, by examining for up to one year the foreign body response and capsular fibrosis triggered by miniaturized or full-scale clinically approved breast implants with different surface topography (average roughness, 0-90 µm) placed in the mammary fat pads of mice or rabbits, respectively, we show that surface topography mediates immune responses to the implants. We also show that the surface surrounding human breast implants collected during revision surgeries also differentially alters the individual's immune responses to the implant. Moreover, miniaturized implants with an average roughness of 4 µm can largely suppress the foreign body response and fibrosis (but not in T-cell-deficient mice), and that tissue surrounding these implants displayed higher levels of immunosuppressive FOXP3+ regulatory T cells. Our findings suggest that, amongst the topographies investigated, implants with an average roughness of 4 µm provoke the least amount of inflammation and foreign body response.

7.
J Urol ; 205(5): 1481-1482, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33656357
8.
Neurourol Urodyn ; 40(1): 137-146, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33606304

RESUMO

AIMS: To investigate the effect of losartan on preventing bladder fibrosis and protecting renal function in rats with neurogenic paralysis bladder (NPB). MATERIALS AND METHODS: Rats were assigned to the transecting spinal nerves group (TSNG), transecting spinal nerves + losartan group (LSTG), and control group (CG). On Day 32 postsurgery, bladder capacity (BC), bladder compliance (ΔC), bladder leakage pressure (Pves.leak ) of TSNG and LSTG while BC, ΔC, and bladder threshold pressure (Pves.thre ) of CG were measured by cystometry in each cohort. Renal function and the expression quantity of Angiotensin Ⅱ (Ang II) in blood were detected, in addition Ang II, Ang II Type 1 receptor (AT1), transformation growth factor ß1 (TGFß1), Collagen Ⅲ, and collagen fibrin in the bladder tissue were detected too. RESULTS: ΔC in TSNG and LSTG decreased significantly compared to the CG. Pves.leak in TSNG and LSTG were significantly higher than Pves.thre in CG. Renal function of both TSNG and LSTG decreased significantly compared with the CG, but renal function in LSTG was better than in TSNG. Ang Ⅱ in blood and bladder tissue in TSNG and LSTG increased significantly compared with CG. AT1 was expressed in the bladder tissue of all rats. The TGFß1, Collagen Ⅲ, and collagen fibrin expression level increased significantly in TSNG compared with LSTG and CG, while these levels were not significantly different between CG and LSTG. CONCLUSION: Losartan might prevent NPB fibrosis by stopping the upregulated signaling of Ang II/AT1/TGFß1 and consequently may reduce kidney damage from occurring.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Fibrose/tratamento farmacológico , Losartan/uso terapêutico , Bexiga Urinaria Neurogênica/tratamento farmacológico , Bexiga Urinária/efeitos dos fármacos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Modelos Animais de Doenças , Losartan/farmacologia , Masculino , Ratos , Ratos Sprague-Dawley
9.
J Pediatr Urol ; 17(3): 290.e1-290.e7, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33622629

RESUMO

INTRODUCTION: Relative Energy Deficiency in Sport (RED-S) is a clinical syndrome that includes the many complex health and performance consequences of low energy availability (EA) in athletes, when there is insufficient caloric intake to meet exercise-related energy expenditure and to support basic physiologic functions. There is a high prevalence of urinary incontinence (UI) in female athletes and it is more common in female athletes than non-athletes. The objective of this study was to determine if low EA is associated with UI in a population of adolescent and young adult female athletes and to evaluate for an association between sport categories and UI. MATERIAL AND METHODS: 1000 nulliparous female patients, ages 15-30 years, presenting to a sports medicine subspecialty clinic, provided informed consent/assent to participate in a cross-sectional study involving a comprehensive survey, anthropomorphic measurements, and medical record review. Low EA was defined as meeting ≥1 criterion: self-reported history of eating disorder/disordered eating (ED/DE), and/or a high score on the Brief Eating Disorder in Athletes Questionnaire (BEDA-Q), and/or a high score on the Eating Disorder Screen for Primary Care (ESP). UI was assessed using questions adapted from the International Consultation on Incontinence-Urinary Incontinence Short Form (ICIQ-UI-SF), questions regarding timing of UI onset/duration, and a binary question regarding UI during sport activities. A total of 36 sport types were included in the survey and sub-divided into categories. RESULTS AND DISCUSSION: Of the 1000 female athletes surveyed, 165 (16.5%) reported a history of experiencing UI during athletic activities. ICIQ- UI-SF responses indicated that 14% (137/1000) of the cohort experienced slight incontinence, 4% (35/1000) moderate incontinence, and 2 athletes experienced severe incontinence. There was a significant difference between UI categories in age (p = 0.01), low EA (p < 0.001), and sport category (p < 0.001). Females who had low EA had twice the likelihood (OR = 1.97; 95% CI = 1.39 to 2.81; p < 0.001) of UI compared to those with adequate EA, controlling for sports category and menstrual dysfunction. Females who participated in high impact sports were 4.5 times more likely (OR = 4.47; 95% CI = 2.29 to 8.74; p < 0.001) to have had UI compared to females who participated in ball sports, controlling for EA and menstrual dysfunction. CONCLUSIONS: UI during athletic activities is a common problem among nulliparous adolescent and young adult female athletes, occurring in 16.5% of female athletes surveyed. UI was significantly associated with low EA across all sport categories. Sport type was significantly associated with UI, with the highest impact sport group demonstrating a higher prevalence and symptom severity compared to other sport categories.


Assuntos
Esportes , Incontinência Urinária , Adolescente , Adulto , Atletas , Estudos Transversais , Feminino , Humanos , Prevalência , Fatores de Risco , Inquéritos e Questionários , Incontinência Urinária/epidemiologia , Incontinência Urinária/etiologia , Adulto Jovem
10.
Am J Hum Genet ; 107(4): 727-742, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32891193

RESUMO

Congenital anomalies of the kidney and urinary tract (CAKUT) constitute one of the most frequent birth defects and represent the most common cause of chronic kidney disease in the first three decades of life. Despite the discovery of dozens of monogenic causes of CAKUT, most pathogenic pathways remain elusive. We performed whole-exome sequencing (WES) in 551 individuals with CAKUT and identified a heterozygous de novo stop-gain variant in ZMYM2 in two different families with CAKUT. Through collaboration, we identified in total 14 different heterozygous loss-of-function mutations in ZMYM2 in 15 unrelated families. Most mutations occurred de novo, indicating possible interference with reproductive function. Human disease features are replicated in X. tropicalis larvae with morpholino knockdowns, in which expression of truncated ZMYM2 proteins, based on individual mutations, failed to rescue renal and craniofacial defects. Moreover, heterozygous Zmym2-deficient mice recapitulated features of CAKUT with high penetrance. The ZMYM2 protein is a component of a transcriptional corepressor complex recently linked to the silencing of developmentally regulated endogenous retrovirus elements. Using protein-protein interaction assays, we show that ZMYM2 interacts with additional epigenetic silencing complexes, as well as confirming that it binds to FOXP1, a transcription factor that has also been linked to CAKUT. In summary, our findings establish that loss-of-function mutations of ZMYM2, and potentially that of other proteins in its interactome, as causes of human CAKUT, offering new routes for studying the pathogenesis of the disorder.


Assuntos
Proteínas de Ligação a DNA/genética , Epigênese Genética , Fatores de Transcrição Forkhead/genética , Mutação , Proteínas Repressoras/genética , Fatores de Transcrição/genética , Sistema Urinário/metabolismo , Anormalidades Urogenitais/genética , Proteínas de Anfíbios/antagonistas & inibidores , Proteínas de Anfíbios/genética , Proteínas de Anfíbios/metabolismo , Animais , Estudos de Casos e Controles , Criança , Pré-Escolar , Proteínas de Ligação a DNA/metabolismo , Família , Feminino , Fatores de Transcrição Forkhead/metabolismo , Heterozigoto , Humanos , Lactente , Larva/genética , Larva/crescimento & desenvolvimento , Larva/metabolismo , Masculino , Camundongos , Camundongos Knockout , Morfolinos/genética , Morfolinos/metabolismo , Linhagem , Ligação Proteica , Proteínas Repressoras/metabolismo , Fatores de Transcrição/metabolismo , Sistema Urinário/anormalidades , Anormalidades Urogenitais/metabolismo , Anormalidades Urogenitais/patologia , Sequenciamento Completo do Exoma , Xenopus
11.
Genet Med ; 22(10): 1673-1681, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32475988

RESUMO

PURPOSE: Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease in childhood and adolescence. We aim to identify novel monogenic causes of CAKUT. METHODS: Exome sequencing was performed in 550 CAKUT-affected families. RESULTS: We discovered seven FOXC1 heterozygous likely pathogenic variants within eight CAKUT families. These variants are either never reported, or present in <5 alleles in the gnomAD database with ~141,456 controls. FOXC1 is a causal gene for Axenfeld-Rieger syndrome type 3 and anterior segment dysgenesis 3. Pathogenic variants in FOXC1 have not been detected in patients with CAKUT yet. Interestingly, mouse models for Foxc1 show severe CAKUT phenotypes with incomplete penetrance and variable expressivity. The FOXC1 variants are enriched in the CAKUT cohort compared with the control. Genotype-phenotype correlations showed that Axenfeld-Rieger syndrome or anterior segment dysgenesis can be caused by both truncating and missense pathogenic variants, and the missense variants are located at the forkhead domain. In contrast, for CAKUT, there is no truncating pathogenic variant, and all variants except one are located outside the forkhead domain. CONCLUSION: We thereby expanded the phenotype of FOXC1 pathogenic variants toward involvement of CAKUT, which can potentially be explained by allelism.


Assuntos
Anormalidades do Olho , Sistema Urinário , Criança , Fatores de Transcrição Forkhead/genética , Heterozigoto , Humanos , Rim , Fenótipo
12.
Neurourol Urodyn ; 39(4): 1178-1184, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32203630

RESUMO

AIMS: No one has assessed urodynamic studies (UDS) to determine those steps that elicit the greatest anxiety, distress, and pain in children. We sought to systematically evaluate a child's UDS experience to mollify these reactions. METHODS: Prospective study involving children aged ≥5 undergoing UDS over a 6-month period (from 10 December 2018 to 22 May 2019). Upon arrival, patients completed a visual analog scale for anxiety (VAS-A, 0-10) about the upcoming procedure. A research assistant assessed the patient's behavior during each major step of UDS using a validated brief behavioral distress scale. Nursing staff also obtained patients' pain ratings (0-10) for these key elements. Immediately after UDS, each child completed a posttest VAS-A along with a survey about the UDS experience. RESULTS: A total of 76 UDS were observed; almost half included sphincter needle electromyography (EMG). Mean patient VAS-A scores were 2.3 before UDS, compared to 0.8 afterward (P < .001). The highest proportion of distressful behaviors were observed during EMG needle (31%) and urethral catheter (29%) insertion, in agreement with the highest mean pain scores of 3.2 and 2.7, respectively. Fifty-four percent of children reported not being completely aware of what was going to happen before the procedure and 50% of those patients exhibited at least one interfering or potentially interfering behavior. Similarly, 60% of children with no prior history of UDS exhibited at least one interfering or potentially interfering behavior. CONCLUSIONS: EMG needle and urethral catheter placement, initial urodynamic testing and not knowing what to expect were associated with greater pain and distress during pediatric UDS.


Assuntos
Ansiedade/fisiopatologia , Dor/fisiopatologia , Uretra/fisiopatologia , Urodinâmica/fisiologia , Adolescente , Adulto , Ansiedade/psicologia , Criança , Pré-Escolar , Eletromiografia , Feminino , Humanos , Masculino , Dor/psicologia , Estudos Prospectivos , Inquéritos e Questionários , Escala Visual Analógica , Adulto Jovem
13.
Am J Hum Genet ; 105(6): 1286-1293, 2019 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-31708116

RESUMO

Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease in the first three decades of life, and in utero obstruction to urine flow is a frequent cause of secondary upper urinary tract malformations. Here, using whole-exome sequencing, we identified three different biallelic mutations in CHRNA3, which encodes the α3 subunit of the nicotinic acetylcholine receptor, in five affected individuals from three unrelated families with functional lower urinary tract obstruction and secondary CAKUT. Four individuals from two families have additional dysautonomic features, including impaired pupillary light reflexes. Functional studies in vitro demonstrated that the mutant nicotinic acetylcholine receptors were unable to generate current following stimulation with acetylcholine. Moreover, the truncating mutations p.Thr337Asnfs∗81 and p.Ser340∗ led to impaired plasma membrane localization of CHRNA3. Although the importance of acetylcholine signaling in normal bladder function has been recognized, we demonstrate for the first time that mutations in CHRNA3 can cause bladder dysfunction, urinary tract malformations, and dysautonomia. These data point to a pathophysiologic sequence by which monogenic mutations in genes that regulate bladder innervation may secondarily cause CAKUT.


Assuntos
Doenças do Sistema Nervoso Autônomo/etiologia , Rim/anormalidades , Mutação , Receptores Nicotínicos/genética , Sistema Urinário/anormalidades , Anormalidades Urogenitais/etiologia , Adulto , Doenças do Sistema Nervoso Autônomo/genética , Doenças do Sistema Nervoso Autônomo/patologia , Feminino , Seguimentos , Humanos , Rim/patologia , Masculino , Linhagem , Prognóstico , Sistema Urinário/patologia , Anormalidades Urogenitais/genética , Anormalidades Urogenitais/patologia , Adulto Jovem
14.
Neurourol Urodyn ; 38(5): 1423-1429, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30998267

RESUMO

AIMS: A pilot survey shows that primary nocturnal enuresis (PNE) prevalence has increased significantly during the past decade in Mainland China. Whether it is related to the delay of elimination communication (EC) is unclear. This study retrospectively investigated the influence of delayed EC on the PNE prevalence in children and adolescents in mainland China. METHODS: A cross-sectional study of PNE prevalence was performed by distributing 19 500 anonymous self-administered questionnaires to parents in five provinces of mainland China from July 2017 to October 2017. The questionnaires included sociodemographic data, family caregivers' information, and details about the disposable diapers (DD) usage, EC commencement date, psychological disorders, lower urinary tract symptoms, and family history of PNE in children and adolescents. The 2017 PNE prevalence was compared with that of 2006 in Mainland China. RESULTS: The total response rate was 97.04% (18 631 of 19 500) and 92.39% (18 016 of 19 500) qualified for statistical analysis. The PNE prevalence in 2017 has increased significantly compared to that of 2006 (7.30% vs 4.07%, P < 0.001). The PNE prevalence in children with EC starting before 6 months of age was significantly lower than those who start after 12 months of age. The longer DD were used and the later the beginning of EC, the higher the PNE prevalence was found. CONCLUSIONS: The PNE prevalence in Mainland China has increased significantly during the past 10 years. A longer use of DD and later onset of EC may be risk factors for PNE.


Assuntos
Enurese Noturna/epidemiologia , Treinamento no Uso de Toaletes , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pais , Prevalência , Estudos Retrospectivos , Inquéritos e Questionários
15.
16.
Neurourol Urodyn ; 37(8): 2306-2310, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30203421

RESUMO

AIMS: To introduce the standard procedure of cystometry and interpretation of the results in children. METHODS: The literature on cystometry in children in PubMed for the last 20 years was reviewed. The updated knowledge regarding indication, preparation, technique, and interpretation of cystometry in children were summarized. RESULTS: Filling cystometry is the core content of a paediatric urodynamic study. In this section, the technique for performing cystometry is introduced in details. Emphasis is placed on correctly setting up the equipment according to ICS and ICCS guidelines, using appropriate terminology, providing indications for its performance with specific considerations for children, and proper interpretation of results. CONCLUSIONS: Cystometry can be used in children including newborn to evaluate lower urinary tract dysfunction.


Assuntos
Bexiga Urinária/fisiopatologia , Urodinâmica , Criança , Cistografia , Feminino , Humanos , Recém-Nascido , Masculino
17.
Biol Blood Marrow Transplant ; 24(12): 2418-2424, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30055351

RESUMO

Human studies have shown loss of diversity of the gut microbiome following hematopoietic stem cell transplantation (HSCT) in association with significant gut injury caused by the preparative regimen. Prolonged antibiotic use worsens loss of microbiome diversity and increases risk of complications such as graft-versus-host disease (GVHD). Our data support the hypothesis that loss of intestinal commensals that produce short-chain fatty acids (SCFAs) may increase dysbiosis. Here, we report an extensive longitudinal examination of changes in the luminal SCFAs in children undergoing allogeneic HSCT, and the relationship of those changes to the microbiota and antibiotic exposure. We found significant and progressive alterations in butyrate, and in additional SCFAs in stool in the first 14 days after transplant, a finding not observed in published mouse studies. SCFA levels were lower in children receiving antibiotics with activity against anaerobic organisms. Moreover, day 14 post-HSCT butyrate and propionate levels are lower in children who went on to develop GVHD, although our disease population was small. These data provide insight into the mechanism of prior observations that loss of diversity and increased antibiotic use are associated with GVHD following HSCT. Our findings offer potential modifiable targets to reduce risk of GVHD and improve survival after HSCT.


Assuntos
Antibacterianos/efeitos adversos , Ácidos Graxos Voláteis/efeitos adversos , Adolescente , Adulto , Antibacterianos/farmacologia , Criança , Pré-Escolar , Ácidos Graxos Voláteis/farmacologia , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Lactente , Recém-Nascido , Masculino , Adulto Jovem
18.
Neurourol Urodyn ; 37(8): 2311-2314, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29931789

RESUMO

AIMS: To introduce the standard procedure and results interpretation of pressure/flow study (PFS) in children. METHODS: The literature on PFS in children in PubMed for the last 20 years was reviewed. The updated knowledge on PFS in children in children regarding indication, preparation, technique, and interpretation were summarized. RESULTS: This educational module explains when and how to do a PFS and how to analyze the results. All requirements and instructions for the PFS in children described in this document follow ICS reports on Good Urodynamic Practice and urodynamic equipment performance as well as guidelines from the ICCS. PFS can be obtained subsequent to filling cystometry with no specific additional equipment (apart from a flowmeter) or patient preparation needed. It requires both vesical and intra-abdominal pressures being recorded. Information from clinical history, physical examination, voiding diaries, and free uroflowmetry with or without perineal patch EMG and pertinent imaging results should be available before undertaking urodynamic testing. CONCLUSIONS: Following ICS and ICCS guidelines, PFS is an easy procedure and a useful tool to provide information on voiding function in children.


Assuntos
Transtornos Urinários/fisiopatologia , Urodinâmica , Criança , Humanos , Pressão , Reologia , Bexiga Urinária/fisiopatologia , Micção/fisiologia , Transtornos Urinários/diagnóstico
19.
J Pediatr Urol ; 14(6): 544.e1-544.e7, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29909988

RESUMO

INTRODUCTION: Stress urinary incontinence (SUI) is common among older multiparous females but rarely reported in active, young girls. OBJECTIVES: Our hypothesis is: physically active adolescent females develop pelvic floor laxity demonstrable on upright VCUG. Our objectives are to (1) increase awareness of SUI in young females, (2) test our hypothesis with an upright VCUG, and (3) report effectiveness of step-wise management. STUDY DESIGN: A retrospective review was performed of nulliparous girls with only SUI seen from 2000 to 2015, who were evaluated with upright voiding cystourethrography (VCUG) (bladder descent defined as ≥2 cm drop of bladder neck below pubic ramus at capacity). Data collection included level of physical activity, physical examination, BMI and Z-scores, urodynamics, management, and treatment response. Standard urotherapy (SUT) (timed voiding, proper diet, adequate fluids, bowel management) and biofeedback therapy (BFT) was initiated. Fisher exact test was used to calculate 'p' values. RESULTS: Thirty-three females (median age 15.1 years, range 5.5-20.3) were identified who underwent an upright VCUG; 20 had bladder neck descent (Fig.). Of these 20, 15 (75%) were involved in strenuous activity, whereas only three of 13 (23%) without descent engaged in intense athletics. No differences were noted in median BMI and Z-score with strenuous activity (21.1 (15.2-26.7) and 0.31 (-0.9-1.94)), respectively, versus patients without (21.3 (15.8-33.5) and 0.62 (-0.0-2.38)). Average follow-up for all was 16.6 months (range 0.4-102.2). Of 20 demonstrating bladder neck descent, three did not complete therapy and were lost to follow-up. Only six of these 17 became dry. Of the remaining 11, eight underwent surgery: Burch colposuspension (5), fascial sling (2), Coaptite to the bladder neck (1), and an artificial urinary sphincter (1). This latter girl had a failed Burch colposuspension 1 year previously. All surgical patients are dry. Of 13 without bladder descent on VCUG, five did not complete therapy and were lost to follow-up. The remaining eight were managed non-surgically; seven were fully dry at last follow-up. Overall, 13 of 25 (52%) achieved dryness. SUT and BFT were more effective in those without, than in those with bladder descent (87.5% vs. 35.3%, p = 0.0302, Fisher exact test). DISCUSSION AND CONCLUSIONS: Physically active, nulligravid girls with SUI can be efficaciously diagnosed on upright VCUG. They should be considered for non-surgical therapy but will likely require bladder neck elevating surgery. Non-surgical therapy works for those with minimal bladder descent on cystography.


Assuntos
Distúrbios do Assoalho Pélvico/complicações , Incontinência Urinária/etiologia , Adolescente , Criança , Pré-Escolar , Cistografia , Feminino , Humanos , Debilidade Muscular/complicações , Distúrbios do Assoalho Pélvico/diagnóstico por imagem , Estudos Retrospectivos , Incontinência Urinária/diagnóstico por imagem , Adulto Jovem
20.
Int Urol Nephrol ; 50(3): 441-449, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29299824

RESUMO

PURPOSE: To investigate the correlation between urethral instability (URI) and overactive bladder (OAB) in children. METHODS: We retrospectively investigated 126 children with OAB and 36 children without OAB using synchro-cystourethrometry. The prevalence of detrusor overactivity (DO) and URI, and the diagnostic sensitivity of DO alone and DO combined with URI, was compared. The OAB children with URI voluntarily received transcutaneous electrical pudendal nerve stimulation with anisodamine (stimulation group, SG) or anisodamine alone (non-stimulation group, NSG). The effectiveness of treatment was evaluated. Average voided volume (AVV), maximum voided volume (MVV), and number of voids per day (NV) were collected and analyzed. RESULTS: In OAB children, the prevalence of DO and URI was 51.6 and 32.5%, respectively. The prevalence of URI was 5.6% in controls. The prevalence of URI was significantly higher in OAB children. The diagnostic sensitivity and Youden index of DO combined with URI were higher than DO alone. In SG, 45.7% of children were cured, with a ≥ 50% improvement rate of 82.9%, while no child was cured, with a ≥ 50% improvement rate of 36.8% in NSG. A significant increase in AVV and MVV together, with a decrease in NV, was seen in SG. There was a significant difference in visual analogue scale values between SG and NSG (P < 0.01). CONCLUSIONS: Urethral instability plays an essential role in the pathogenesis and progression of OAB in children. Synchro-cystourethrometry is a useful urodynamic technology to precisely diagnose OAB, and transcutaneous electrical pudendal nerve stimulation may be an effective treatment for OAB children induced by URI.


Assuntos
Agonistas alfa-Adrenérgicos/uso terapêutico , Alcaloides de Solanáceas/uso terapêutico , Estimulação Elétrica Nervosa Transcutânea , Doenças Uretrais/terapia , Bexiga Urinária Hiperativa/diagnóstico , Bexiga Urinária Hiperativa/terapia , Criança , Terapia Combinada , Feminino , Humanos , Masculino , Nervo Pudendo , Estudos Retrospectivos , Doenças Uretrais/complicações , Doenças Uretrais/fisiopatologia , Bexiga Urinária/fisiopatologia , Bexiga Urinária Hiperativa/etiologia , Bexiga Urinária Hiperativa/fisiopatologia , Micção , Urodinâmica
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