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1.
Urology ; 135: 38-43, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31600558

RESUMO

OBJECTIVE: To evaluate differences in adverse events (AE) in asymptomatic patients with a positive urine dip (UD) at time of intradetrusor onabotulinumtoxinA (BTX-A) injection vsthose with a defined negative UD. MATERIALS AND METHODS: All intradetrusor BTX-A injections were retrospectively reviewed at a single institution between 2016 and 2018. Exclusion criteria included an indwelling catheter, recent positive urine culture, recent antibiotic course, or absence of UD on the day of injection. A positive UD was defined using 7 different definitions with varying combinations of any level of positive blood, leukocyte esterase, or nitrite. Negative UDs were defined those excluded from the positive UD group. We compared multiple positive UD-defined groups to their respective negative UD cohorts with regards to outcomes and demographics. RESULTS: A total of 212 patients underwent 335 cycles of BTX-A injections over a 2-year period. The average age was 65 years (range: 21-90). The majority received 100 units (73%) of BTX-A for a non-neurogenic diagnosis (73%). The overall rate of AEs, urinary tract infection, and urinary retention was 14.6%, 9%, and 3%, respectively. In all groups, the most common AE was urinary tract infection followed by urinary retention. There were no major Clavien-Dindo-defined complications. There was no statistically significant difference in the total or categorical AE rates between positive and negative UD groups using all 7 definitions of a positive UD (P = .05-1.0). CONCLUSION: These data do not support the practice of obtaining a preprocedure UD in asymptomatic patients undergoing intradetrusor BTX-A injection for any indication; test results are unable to predict outcomes or AEs.


Assuntos
Toxinas Botulínicas Tipo A/efeitos adversos , Fármacos Neuromusculares/efeitos adversos , Bexiga Urinária Hiperativa/tratamento farmacológico , Retenção Urinária/epidemiologia , Infecções Urinárias/epidemiologia , Administração Intravesical , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Assintomáticas/terapia , Toxinas Botulínicas Tipo A/administração & dosagem , Feminino , Humanos , Injeções Intramusculares/efeitos adversos , Injeções Intramusculares/métodos , Masculino , Pessoa de Meia-Idade , Fármacos Neuromusculares/administração & dosagem , Estudos Retrospectivos , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/fisiopatologia , Bexiga Urinária Hiperativa/fisiopatologia , Retenção Urinária/etiologia , Infecções Urinárias/etiologia , Infecções Urinárias/urina , Urodinâmica/efeitos dos fármacos , Adulto Jovem
2.
Crit Care Resusc ; 21(4): 258-64, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31778632

RESUMO

OBJECTIVE: To compare the physiological and biochemical effects of a single intravenous dose of furosemide or acetazolamide in critically ill patients. DESIGN: Single centre, pilot randomised controlled trial. SETTING: Large tertiary adult intensive care unit (ICU). PARTICIPANTS: Twenty-six adult ICU patients deemed to require diuretic therapy. INTERVENTION: Single dose of intravenous 40 mg furosemide or 500 mg acetazolamide. MAIN OUTCOME MEASURES: Data were collected on urine output, cumulative fluid balance, and serum and urine biochemistry for 6 hours before and 6 hours after diuretic administration. RESULTS: Study patients had a median age of 55 years (IQR, 50-66) and median APACHE III score of 44 (IQR, 37-52). Furosemide caused a much greater increase in-urine output and much greater median mass chloride excretion (121.7 mmol [IQR, 81.1-144.6] v 23.3 mmol [IQR, 20.4-57.3]; P < 0.01) than acetazolamide. Furosemide also resulted in a progressively more negative fluid balance while acetazolamide resulted in greater alkalinisation of the urine (change in median urinary pH, +2 [IQR, 1.75-2.12] v 0 [IQR, 0-0.5]; P = 0.02). In keeping with this effect, furosemide alkalinised and acetazolamide acidified plasma (change in median serum pH, +0.03 [IQR, 0.01-0.04] v -0.01 [IQR, -0.04 to 0]; P = 0.01; change in median serum HCO3-, +1.5 mmol/L [IQR, 0.75-2] v -2 mmol/L [IQR, -3 to 0]; P < 0.01). CONCLUSIONS: Furosemide is a more potent diuretic and chloriuretic agent than acetazolamide in critically ill patients, and achieves a threefold greater negative fluid balance. Compared with acetazolamide, furosemide acidifies urine and alkalinises plasma. Our findings imply that combination therapy might be a more physiological approach to diuresis in critically ill patients.


Assuntos
Acetazolamida/farmacologia , Acetazolamida/farmacocinética , Estado Terminal/terapia , Diuréticos/farmacologia , Diuréticos/farmacocinética , Furosemida/farmacologia , Furosemida/farmacocinética , Acetazolamida/administração & dosagem , Adulto , Idoso , Diuréticos/administração & dosagem , Eletrólitos/sangue , Furosemida/administração & dosagem , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Projetos Piloto , Resultado do Tratamento , Urodinâmica/efeitos dos fármacos , Equilíbrio Hidroeletrolítico/efeitos dos fármacos
3.
Strahlenther Onkol ; 195(10): 934-939, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31363801

RESUMO

PURPOSE: The urinary bladder is one major organ at risk in radiotherapy of pelvic malignancies. The radiation response manifests in early and chronic changes in bladder function. These are based on inflammatory effects and changes in urothelial cell function and proliferation. This study evaluates the effect of bortezomib as an anti-proliferative and anti-inflammatory compound in an established mouse bladder model. The early radiation-induced bladder dysfunction in the mouse occurs in two phases during the first month after irradiation (phase I: day 0-15, phase II: days 16-30). MATERIALS AND METHODS: Daily bortezomib injections (0.02 mg/ml, subcutaneously) were administered between days 0-15 or 15-30 in separate groups. Single graded radiation doses were administered in five dose groups. Cystometry was carried out before (individual control) and during the first month after irradiation. When bladder capacity was decreased by ≥50%, mice were considered as responders. Statistical analysis was performed by the SPSS software version 24. RESULTS: Daily bortezomib injections between days 0-15 resulted in a significant decrease in responders for phase I. There was no significant effect with daily bortezomib injections between days 16-30. CONCLUSION: Two separate waves of acute radiation-induced urinary bladder dysfunction have distinct mechanisms that need further biological studies.


Assuntos
Bortezomib/farmacologia , Lesões Experimentais por Radiação/tratamento farmacológico , Bexiga Urinária/efeitos da radiação , Animais , Relação Dose-Resposta à Radiação , Esquema de Medicação , Feminino , Humanos , Injeções Subcutâneas , Camundongos , Camundongos Endogâmicos C3H , Tamanho do Órgão/efeitos dos fármacos , Tamanho do Órgão/efeitos da radiação , Órgãos em Risco/efeitos da radiação , Bexiga Urinária/efeitos dos fármacos , Urodinâmica/efeitos dos fármacos , Urodinâmica/efeitos da radiação
4.
Urology ; 133: 72-77, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31465791

RESUMO

OBJECTIVE: To assess whether intraurethral anesthesia decreased voiding efficiency (VE), reduced catheterization pain, and impacted urodynamic parameters in healthy adult females. METHODS: In a randomized, double-blind, placebo-controlled trial, participants received two 5 mL doses of either intraurethral aqueous gel or 4% lidocaine gel. The primary outcome was VE during randomized condition uroflow, defined as voided volume/(voided volume + residual volume). The secondary outcomes were pain during catheterization and to confirm previously reported pressure-flow changes. A sample size of 10 per group was planned to detect a clinically significant decrease in VE with a power (1-ß) of 0.99. RESULTS: From October to December 2018, 23 women were screened and 18 were randomized to receive placebo (n = 10) or lidocaine (n = 8). Baseline uroflow VE was similar between the placebo and lidocaine groups (88 ± 6.6% vs 91 ± 5.8%, P = .33). After study drug administration, the changes in VE (post-pre) were similar between placebo and lidocaine groups (-5.4 ± 14% vs 1.7 ± 6.4%, P = .21). Visual analog scores were similar following catheterizations (26.7 ± 12.8 mm vs 36.9 ± 26.8 mm, P = .34). The lidocaine group exhibited lower average flow rates per voided volume (0.04 ± 0.02 s-1 vs 0.02 ± 0.01 s-1, P = .04). CONCLUSION: Intraurethral administration of 4% lidocaine did not decrease VE compared to placebo and did not change pain scores following catheterization. In the lidocaine group, the average flow rate per voided volume was lower. The decrease in flow rate after local anesthesia to the urethra may indicate that urethral sensory feedback contributes to voiding in human micturition.


Assuntos
Anestésicos Locais/administração & dosagem , Lidocaína/administração & dosagem , Dor/prevenção & controle , Cateterismo Urinário , Micção/efeitos dos fármacos , Urodinâmica/efeitos dos fármacos , Administração Tópica , Adulto , Anestésicos Locais/farmacologia , Método Duplo-Cego , Feminino , Humanos , Lidocaína/farmacologia , Uretra , Cateterismo Urinário/efeitos adversos
5.
Low Urin Tract Symptoms ; 11(4): 248-254, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31250566

RESUMO

The aim of this study was to determine whether aging-related detrusor underactivity (DU) involves a decrease in 5-hydroxytryptamine (5-HT-positive)-expressing urethral cells and whether 5-HT stimulation of urethral sensory fibers improves detrusor function. Cystometries were performed in young (6 months) and aged (18-24 months) female Wistar rats. Aged rats with voiding contractions (VC) that were 2SD below the mean of those in young rats were considered to have DU. Bladder voiding efficiency (BVE) was calculated during saline or 5-HT solution cystometries. Rats were perfusion-fixed with a fixative solution (paraformaldehyde, PFA 4%) through the circulatory system and the urethra sectioned to count the number of 5-HT-immunoreactive (IR) cells. Isovolumetric cystometry was performed while irrigating the urethra with saline or 5µM-HT solution. Two-tailed unpaired t tests were used to determine the significance of differences. In aged DU rats, the mean (±SD) VC frequency was 0.24 ± 0.07 per minute, with an amplitude of 15 ± 3 cm H2 O. The mean (±SD) number of 5-HT-IR cells in the urethra of aged DU and young rats was 90 ± 11 and 182 ± 25, respectively (P < 0.01). 5-HT improved the mean (±SD) BVE of aged DU rats from 49 ± 3% to 78 ± 2% (P < 0.001). In isovolumetric cystometries, detrusor pressure during irrigation of the urethra with saline was 18 ± 1 cm H2 O, compared with 39 ± 2 cm H2 O during irrigation with 5-HT solution (P < 0.05). In rats, DU associated with aging is accompanied by a decrease in the number of 5-HT-positive cells. The results suggest that decreased 5-HT availability decreases urethral sensory fiber excitation, leading to a decrease the number of effective VC.


Assuntos
Serotonina/uso terapêutico , Uretra/efeitos dos fármacos , Bexiga Inativa/tratamento farmacológico , Envelhecimento/fisiologia , Animais , Feminino , Ratos , Ratos Wistar , Serotonina/metabolismo , Uretra/citologia , Uretra/fisiopatologia , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/fisiopatologia , Bexiga Inativa/metabolismo , Bexiga Inativa/fisiopatologia , Urodinâmica/efeitos dos fármacos
6.
Toxicol Lett ; 311: 27-36, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31039415

RESUMO

Methotrexate (MTX) is a derivate of folic acid, commonly used as an anchor drug for the treatment and management of malignant diseases and autoimmune disorders. However, nephrotoxicity is an important drawback of MTX therapy. Unfortunately, there are not enough studies reporting the nature of the renal failure induced by MTX. Thus, the aim of this study was to evaluate the time course of renal handling of water and electrolytes in male Wistar rats, after the exposure to a unique dose of MTX (80 mg/kg b.w.). Experiments were carried out at day 2, day 4, day 8 and day 14 after MTX administration. Several parameters of kidney function related to water and electrolytes handling were evaluated. Renal expression and urinary excretion of aquaporin-2 (AQP2) and Na-K-2Cl-cotransporter (NKCC2) were determined by Western blotting. MTX produced alterations on water handling on the second day after treatment, showing a significant increase in solute free water reabsorption which might be mediated by the increased expression of AQP2 in apical membranes. On the other hand, MTX produced alterations on electrolytes handling on the fourth day after treatment, showing a significant decrease of sodium chloride excretion, mediated at least in part, by the increase renal expression of NKCC2. These results provide valuable information to clinical practice in order to be able to find therapeutic targets that diminish adverse effects and health deterioration. Moreover, MTX treatment altered AQP2 and NKCC2 urinary excretion allowing postulating these transporters as potential biomarkers of MTX induced nephrotoxicity.


Assuntos
Aquaporina 2/metabolismo , Eletrólitos/metabolismo , Nefropatias/induzido quimicamente , Túbulos Renais/efeitos dos fármacos , Metotrexato/toxicidade , Reabsorção Renal/efeitos dos fármacos , Membro 1 da Família 12 de Carreador de Soluto/metabolismo , Água/metabolismo , Animais , Biomarcadores/metabolismo , Cloretos/metabolismo , Nefropatias/metabolismo , Túbulos Renais/metabolismo , Masculino , Potássio/metabolismo , Ratos Wistar , Sódio/metabolismo , Fatores de Tempo , Urodinâmica/efeitos dos fármacos
7.
Gynecol Obstet Invest ; 84(5): 472-476, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30897579

RESUMO

AIMS: To determine if findings at urodynamics prognosticate improvements in overactive bladder symptoms among women receiving mirabegron treatment. METHODS: Before treatment, women completed a urodynamic investigation, a micturition diary and the Urinary Distress Inventory (UDI) with the irritative subscale UDIOAB. After 6 months mirabegron treatment, patients were clinically evaluated and completed the UDI. Associations were tested using regression analyses and nonparametric statistics. RESULTS: Testing urodynamic variables for association with treatment effects in multiple linear regression analysis showed that lower volumes at first sensation to void significantly correlated with greater improvement in the UDIOAB after 6 months mirabegron treatment (B = 0.026, 95% CI 0.002-0.049, p = 0.034). Improvements in UDIOAB showed no correlation with presence of nocturia (p = 0.65), previous use of anticholinergics (p = 1), menopausal status (p = 1), any detrusor overactivity during filling (p = 1), phasic detrusor contractions during filling (p = 1), or detrusor overactivity during inhibition (p = 1). CONCLUSIONS: We found limited support for clinically relevant associations between findings at urodynamics and subsequent treatment outcomes for mirabegron in routine clinical practice. Our findings do not support the role of these investigations as predictors of outcomes in patients with overactive bladder symptoms.


Assuntos
Acetanilidas/uso terapêutico , Técnicas de Diagnóstico Urológico/estatística & dados numéricos , Tiazóis/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Urodinâmica/efeitos dos fármacos , Agentes Urológicos/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Resultado do Tratamento , Bexiga Urinária/efeitos dos fármacos , Micção/efeitos dos fármacos
8.
Adv Clin Exp Med ; 28(4): 555-567, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30729759

RESUMO

Intra-detrusor injection therapy with onabotulinumtoxinA is generally accepted as a highly effective, minimally invasive and well-tolerated day procedure for patients with refractory overactive bladder (OAB) and neurogenic detrusor overactivity (NDO). The aim of this study was to summarize currently available methods of assessing treatment efficacy and risk factors that may influence the therapeutic effect of this approach. We found that there are discrepancies in the assessment methods. The evaluation of intra-detrusor injections with onabotulinumtoxinA in clinical trials are not always transposable into day-to-day practice. Moreover, the primary endpoints in clinical trials do not explore the entirety of meaningful patient-centered outcomes. Therefore, in daily clinical practice with patients with overactive bladder syndrome, the therapy should be assessed with objective measures (bladder diaries) and patient-oriented outcomes analyzing the quality of life (questionnaires). In neurogenic individuals, therapeutic efficacy should be additionally evaluated with urodynamic studies. Potential risk factors that may influence the treatment outcomes include urodynamically proven detrusor overactivity, elevated maximum detrusor pressure, greater maximum cystometric capacity, impaired bladder compliance, older age, male gender, a higher baseline bother score, previous anticholinergic treatment, and repeated injections with a subsequent decline in efficacy. The risk of intermittent catheterization following injections seems to depend on the etiology of detrusor overactivity, the injected dose, the injection technique, and the definition of significant post-void residual urine requiring catheterization.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/uso terapêutico , Fármacos Neuromusculares/administração & dosagem , Bexiga Urinaria Neurogênica/tratamento farmacológico , Bexiga Urinária Hiperativa/tratamento farmacológico , Incontinência Urinária/tratamento farmacológico , Urodinâmica/efeitos dos fármacos , Toxinas Botulínicas Tipo A/efeitos adversos , Feminino , Humanos , Masculino , Fármacos Neuromusculares/efeitos adversos , Qualidade de Vida , Resultado do Tratamento , Bexiga Urinaria Neurogênica/fisiopatologia , Incontinência Urinária/etiologia
9.
Am J Physiol Renal Physiol ; 316(6): F1133-F1140, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30785353

RESUMO

Chemotherapy-induced hemorrhagic cystitis is characterized by bladder pain and voiding dysfunction caused by hemorrhage and inflammation. Novel therapeutic options to treat hemorrhagic cystitis are needed. We previously reported that systemic administration of the Schistosomiasis hematobium-derived protein H-IPSEH06 (IL-4-inducing principle from Schistosoma mansoni eggs) is superior to three doses of MESNA in alleviating hemorrhagic cystitis (Mbanefo EC, Le L, Pennington LF, Odegaard JI, Jardetzky TS, Alouffi A, Falcone FH, Hsieh MH. FASEB J 32: 4408-4419, 2018). Based on prior reports by others on S. mansoni IPSE (M-IPSE) and additional work by our group, we reasoned that H-IPSE mediates its effects on hemorrhagic cystitis by binding IgE on basophils and inducing IL-4 expression, promoting urothelial proliferation, and translocating to the nucleus to modulate expression of genes implicated in relieving bladder dysfunction. We speculated that local bladder injection of the S. hematobium IPSE ortholog IPSEH03, hereafter called H-IPSEH03, might be more efficacious in preventing hemorrhagic cystitis compared with systemic administration of IPSEH06. We report that H-IPSEH03, like M-IPSE and H-IPSEH06, activates IgE-bearing basophils in a nuclear factor of activated T-cells reporter assay, indicating activation of the cytokine pathway. Furthermore, H-IPSEH03 attenuates ifosfamide-induced increases in bladder wet weight in an IL-4-dependent fashion. H-IPSEH03 relieves hemorrhagic cystitis-associated allodynia and modulates voiding patterns in mice. Finally, H-IPSEH03 drives increased urothelial cell proliferation, suggesting that IPSE induces bladder repair mechanisms. Taken together, H-IPSEH03 may be a potential novel therapeutic to treat hemorrhagic cystitis by basophil activation, attenuation of allodynia, and promotion of urothelial cell proliferation.


Assuntos
Proliferação de Células/efeitos dos fármacos , Cistite/prevenção & controle , Proteínas do Ovo/administração & dosagem , Proteínas de Helminto/administração & dosagem , Hemorragia/prevenção & controle , Fatores Imunológicos/administração & dosagem , Bexiga Urinária/efeitos dos fármacos , Urotélio/efeitos dos fármacos , Administração Intravesical , Animais , Basófilos/efeitos dos fármacos , Basófilos/imunologia , Basófilos/metabolismo , Linhagem Celular , Cistite/induzido quimicamente , Cistite/imunologia , Cistite/metabolismo , Modelos Animais de Doenças , Feminino , Hemorragia/induzido quimicamente , Hemorragia/imunologia , Hemorragia/metabolismo , Humanos , Ifosfamida , Imunoglobulina E/imunologia , Imunoglobulina E/metabolismo , Injeções Intravenosas , Interleucina-4/imunologia , Interleucina-4/metabolismo , Camundongos Endogâmicos C57BL , Fatores de Transcrição NFATC/imunologia , Fatores de Transcrição NFATC/metabolismo , Transdução de Sinais , Bexiga Urinária/imunologia , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , Urodinâmica/efeitos dos fármacos , Urotélio/imunologia , Urotélio/metabolismo , Urotélio/patologia
10.
J Thorac Cardiovasc Surg ; 157(6): 2444-2451, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30745052

RESUMO

OBJECTIVE: A standardized assessment of response to furosemide is predictive of acute kidney injury progression in adults, but a paucity of data exists in pediatric patients. We evaluate furosemide responsiveness in a multicenter cohort of pediatric patients after cardiac surgery. METHODS: Children who underwent cardiac surgery with a Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery score of 3 or greater were retrospectively identified. The first dose of furosemide after surgery was recorded, and hourly urine output for 6 hours was recorded after the index dose. Urine flow rate calculated as urine output per hour was used to predict development of acute kidney injury. RESULTS: A total of 166 patients from 4 institutions (median age, 6.3 months; interquartile range, 0.4-27.7) were included. Acute kidney injury occurred in 54 patients (33%). Compared with those without acute kidney injury, the 2- and 6-hour urine flow rates were significantly lower in patients in whom acute kidney injury developed: 2.9 (0.9-6.5) versus 5.0 (2.5-9.0) mL/kg/h for 2-hour urine flow rate, P = .004, and 2.4 (1.2-4.0) versus 4.0 (2.3-5.9) mL/kg/h for 6-hour flow rate, P = .001. In multivariable regression analysis, 2-hour (odds ratio, 1.2, P = .002) and 6-hour (odds ratio, 1.40, P < .001) urine flow rates were independently associated with acute kidney injury development. Lower urine flow rate at both 2 and 6 hours was also independently associated with longer hospital length of stay. CONCLUSIONS: Lower urine flow rate after furosemide administration, when evaluated in a heterogeneous cohort of children from multiple institutions after pediatric cardiac surgery, was independently associated with subsequent acute kidney injury and longer length of stay. Future prospective studies are needed to validate furosemide responsiveness as a predictor of acute kidney injury.


Assuntos
Lesão Renal Aguda/etiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Diuréticos/farmacologia , Furosemida/farmacologia , Pré-Escolar , Creatinina/sangue , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Urodinâmica/efeitos dos fármacos
11.
J Pediatr Surg ; 54(3): 595-599, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29887168

RESUMO

OBJECTIVE: The purpose of this study is to evaluate the effect of Intravesical Botulinum toxin injection on the symptoms and urodynamic parameters in pediatric patients with idiopathic overactive bladder (iOAB) refractory to medical treatment. MATERIALS AND METHODS: The study was designed as an open-label uncontrolled therapeutic clinical trial. The eligible patients who underwent Intravesical botulinum toxin injection were evaluated before treatment. The evaluation included a 7-day paper bladder diary to assess OAB symptoms (frequency, urgency urinary incontinence (UUI) and nocturnal enuresis (NE)), filling the Arabic International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI short form), and conducting urodynamic study. The Urodynamic parameters obtained were the maximum filling detrusor pressure, cystometric bladder capacity, and compliance. After 12 weeks of the intravesical injection, the patients were revaluated and the results were compared using paired samples t-test. RESULTS: The study enrolled 75 patients. And of those, statistical analysis was done on 46 patients who did follow the study protocols. The mean age was 8.9 years and male to female ratio was 1:4. There was a statistically significant improvement in overactive bladder symptoms and urodynamic parameters in the patient injected with botulinum toxin with minimal side effects. CONCLUSION: The evidence in this study would support the safety and efficacy of Intravesical botulinum toxin injection in children with refractory idiopathic OAB with significant improvement of symptoms, quality of life, as well as urodynamic parameters. TYPE OF STUDY: Open-label uncontrolled therapeutic clinical trial. LEVEL OF EVIDENCE: III.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Fármacos Neuromusculares/administração & dosagem , Bexiga Urinária Hiperativa/tratamento farmacológico , Administração Intravesical , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários , Resultado do Tratamento , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/fisiopatologia , Incontinência Urinária/tratamento farmacológico , Incontinência Urinária/etiologia , Urodinâmica/efeitos dos fármacos
12.
J Formos Med Assoc ; 118(1 Pt 1): 125-133, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29482913

RESUMO

OBJECTIVE: To evaluate the changes in urothelial dysfunction protein expressions in bladder after onabotulinumtoxin injection and correlate that with clinical outcomes in spinal cord injury (SCI) patients. METHODS: Twenty-six patients with neurogenic detrusor overactivity (NDO) and urinary incontinence due to suprasacral SCI were treated with onabotulinumtoxinA 200U detrusor injection. Urodynamic studies and bladder biopsies were obtained at baseline, 3, and 6 months after treatment. Biopsy tissues were investigated for E-cadherin, zonula occludens-1 (ZO-1), mast cell activity, and urothelial cell apoptosis, sensory protein expression including purinergic receptor P2X3, endothelial NOS, inducible NOS, ß3-adrenoceptors, and muscarinic receptors M2 and M3. Differences in functional protein expression between controls and SCI patients and between successful and failed treatment groups were analyzed. RESULTS: SCI patients had significantly lower E-cadherin, higher mast cell activity, increased apoptosis, decreased M3 and eNOS expressions than the controls at baseline. Of the 26 patients, 17 (65%) showed improvement in bladder capacity by >50% at 3 months; however, improvement declined by 6 months after treatment. The urothelial expression of E-cadherin and ZO-1 increased at 3 months but had declined at 6 months. The urothelial sensory protein expression did not change significantly after treatment. M3 receptor density was significantly decreased in SCI patients at baseline and patients with treatment success 3 months after injection (p = 0.01). CONCLUSION: A single injection of onabotulinumtoxinA 200U improved clinical symptoms but did not significantly alter urothelial sensory protein expression. The results imply that a single 200U onabotulinumtoxinA dose might not be adequate for urothelial dysfunction in NDO. IRB: TCGH 098-53.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Traumatismos da Medula Espinal/complicações , Bexiga Urinária Hiperativa/tratamento farmacológico , Urotélio/fisiopatologia , Adulto , Antígenos CD/metabolismo , Caderinas/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Injeções , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento , Bexiga Urinária/patologia , Bexiga Urinária Hiperativa/etiologia , Urodinâmica/efeitos dos fármacos , Urotélio/efeitos dos fármacos , Proteína da Zônula de Oclusão-1/metabolismo
13.
Low Urin Tract Symptoms ; 11(2): O152-O161, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30079630

RESUMO

OBJECTIVE: The aim of this study was to report the final 3-year results from a surveillance study evaluating the safety, efficacy, and persistence of mirabegron for treating overactive bladder (OAB) symptoms. METHODS: Patients who had started mirabegron for the treatment of urinary urgency, daytime frequency, and urgency urinary incontinence symptoms associated with OAB were followed for 3 years. Adverse drug reactions (ADRs), residual urine volume measurements, OAB symptoms, Overactive Bladder Symptom Scores (OABSS), and treatment discontinuations were evaluated prospectively. Persistence was estimated using the Kaplan-Meier method. RESULTS: Of the 1138 patients included in the study (mean ±SD age: 71.9 ± 11.0 years; 574 [50.4%] women), 97 (8.52%) experienced 109 ADRs, with the incidence of ADRs decreasing over time (<1 year: 1.34%-2.37%; ≥1-<2 years: 0.45%-1.60%; ≥2-<3 years: 0.29%-1.10%; 3-monthly interval data). No significant increases in residual urine volume were observed. The investigators considered mirabegron to be an effective treatment for 842 of 1082 (77.8%) patients. Significant decreases in OABSS were reported throughout (P < 0.001), and 321 (65.1%) patients achieved a minimal clinically important change (MCIC) in OABSS. Most patients who achieved an MCIC within ≤1 year continued to maintain an MCIC throughout the study. Treatment persistence rates after 1, 2, and 3 years of mirabegron treatment were 65.8%, 52.9%, and 46.7%, respectively. CONCLUSION: Over 3 years, mirabegron was well tolerated and no cumulative events or delayed ADRs were observed. Mirabegron was an effective treatment with early improvements in OABSS being maintained throughout the treatment period. High persistence was observed after the use of mirabegron.


Assuntos
Acetanilidas/uso terapêutico , Tiazóis/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Agentes Urológicos/uso terapêutico , Acetanilidas/efeitos adversos , Idoso , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Vigilância de Produtos Comercializados , Tiazóis/efeitos adversos , Resultado do Tratamento , Urodinâmica/efeitos dos fármacos , Agentes Urológicos/efeitos adversos
14.
Female Pelvic Med Reconstr Surg ; 25(4): 265-270, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29300256

RESUMO

OBJECTIVES: The aim of the study was to determine whether intraurethral anesthesia decreases voiding efficiency (VE; voided volume/(voided volume + residual volume)) and impacts other urodynamic parameters in healthy female volunteers during urodynamic studies. METHODS: This was a randomized double-blind placebo-controlled study of asymptomatic women aged 18 to 60 years. Subjects completed a visual analog scale and baseline questionnaires to assess pain and lower urinary tract symptoms, respectively. They performed an uninstrumented baseline uroflow, followed by physiologic filling to 250 mL or greater. Subjects were randomized to receive 5 mL of intraurethral aqueous gel or 2% lidocaine gel and then underwent a second uninstrumented uroflow. They then completed complex cystometry, urethral pressure profilometry, and pressure-flow studies. RESULTS: Twenty-three randomized subjects (12 placebo, 11 lidocaine) were included. Baseline uroflow VE was similar between the placebo and lidocaine groups. After study drug administration, VE was not different between groups (89.3 [85.9-93.9] vs 89.5 [82.5-91.7], P = 0.74). There were also no differences between groups in visual analog scale scores, sensation during cystometry, maximum urethral closure pressure, or micturition parameters (maximum detrusor pressure and detrusor pressure at maximum flow). The placebo group had a lower percentage of interrupted flow pattern (0% vs 36%, P = 0.02) and a lower rate of increased electromyographic activity during micturition (25% vs 73%, P = 0.02). CONCLUSIONS: In this pilot study of 23 asymptomatic women, intraurethral administration of lidocaine did not decrease VE compared with placebo. The lidocaine group had a greater percentage of interrupted flow patterns and increased electromyographic activity during micturition.


Assuntos
Anestésicos Locais/farmacologia , Lidocaína/farmacologia , Micção/efeitos dos fármacos , Urodinâmica/efeitos dos fármacos , Adulto , Anestésicos Locais/administração & dosagem , Método Duplo-Cego , Eletromiografia , Feminino , Géis , Humanos , Lidocaína/administração & dosagem , Dor Processual/prevenção & controle , Projetos Piloto , Uretra/efeitos dos fármacos , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/fisiologia , Cateterismo Urinário , Urina , Adulto Jovem
15.
Am J Physiol Renal Physiol ; 316(1): F113-F120, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30353742

RESUMO

Bladder outlet obstruction (BOO) leads to progressive voiding dysfunction. Acutely, obstruction triggers inflammation that drives bladder dysfunction. Over time, inflammation leads to decreased bladder nerve density and increased fibrosis, responsible for eventual decompensation and irreversibility. We have previously shown that BOO triggers inflammation, reduced bladder nerve density and increased fibrosis via activation of the NLRP3 inflammasome in an acutely obstructed (12-day) rat model. However, as BOO progresses, the bladder may become decompensated with an increase in postvoid residual volume and decreased voiding efficiency. Currently, we have examined rat bladder function and nerve densities after chronic BOO to determine whether NLRP3 plays a role in the decompensation at this stage. Four groups were examined: control, sham-operated, BOO, or BOO+gly (glyburide; an NLRP3 inhibitor). After 42 days, bladder weight, inflammation (Evans blue), urodynamics, and nerve density were measured. BOO greatly enhanced bladder weights and inflammation, while inflammation was prevented by glyburide. Voiding pressures were increased, and flow rates decreased in BOO and BOO+gly groups, demonstrating physical obstruction. No difference in frequency or voided volume was detected. However, postvoid residual volumes were greatly increased in BOO rats while BOO+gly rats were not different than controls. Moreover, there was a dramatic decrease in voiding efficiency in the chronic BOO rats, which was prevented with glyburide treatment. Finally, a reduction in nerve density was apparent with BOO and attenuated with glyburide. Together the results suggest a critical role for NLRP3 in mediating bladder decompensation and nerve density during chronic BOO.


Assuntos
Anti-Inflamatórios/farmacologia , Sistema Nervoso Autônomo/efeitos dos fármacos , Cistite/prevenção & controle , Glibureto/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Obstrução do Colo da Bexiga Urinária/tratamento farmacológico , Bexiga Urinária/inervação , Urodinâmica/efeitos dos fármacos , Animais , Sistema Nervoso Autônomo/fisiopatologia , Doença Crônica , Cistite/metabolismo , Cistite/fisiopatologia , Modelos Animais de Doenças , Feminino , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Obstrução do Colo da Bexiga Urinária/metabolismo , Obstrução do Colo da Bexiga Urinária/fisiopatologia
16.
Int Urol Nephrol ; 51(2): 253-260, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30474782

RESUMO

PURPOSE: To demonstrate that phosphodiesterase type 4 (PDE4) inhibitors could potentially treat diabetic bladder dysfunction (DBD) through modulation of the systemic inflammatory response. METHODS: In this 6-week study, 60 female Sprague-Dawley rats were divided into three groups: (i) vehicle-treated control rats; (ii) vehicle-treated streptozocin (STZ)-injected rats; and (iii) roflumilast-treated STZ-injected rats. Oral roflumilast (5 mg/kg/day) was administered during the last 4 weeks of STZ injection to induce diabetes in the test group. At 6 weeks, a urodynamic study was performed in each group. The expression of nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-1ß in detrusor smooth muscle (DSM) was analyzed using quantitative reverse transcription-polymerase chain reaction and Western blotting. RESULTS: A significant decrease in bodyweight and significant increases in bladder weight and blood glucose level were observed in the diabetic rats and were not ameliorated by roflumilast treatment. Cystometry showed the increased bladder capacity, voiding volume, residual urine volume, and voiding interval in the diabetic rats and the prevention of these changes by roflumilast. These changes were accompanied by significantly enhanced expression of NF-κB, TNF-α, IL-6, and IL-1ß in DSM tissue from diabetic rats. Furthermore, roflumilast attenuated the expression of inflammatory factors in DSM tissue. CONCLUSIONS: Oral treatment with roflumilast in diabetic rats improves bladder function and inhibits the expression of inflammatory factors in DSM tissue, indicating that PDE4 is a potential therapeutic target for DBD.


Assuntos
Aminopiridinas/farmacologia , Benzamidas/farmacologia , Cistite , Complicações do Diabetes , Urodinâmica/efeitos dos fármacos , Animais , Ciclopropanos/farmacologia , Cistite/tratamento farmacológico , Cistite/etiologia , Cistite/imunologia , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/imunologia , Diabetes Mellitus Experimental , Feminino , Inflamação/tratamento farmacológico , Inflamação/imunologia , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , NF-kappa B/metabolismo , Inibidores da Fosfodiesterase 4/farmacologia , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento , Fator de Necrose Tumoral alfa/metabolismo
17.
Neurourol Urodyn ; 38(2): 615-624, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30549314

RESUMO

AIMS: To investigate the effects of injecting RNA interference (RNAi) lentiviruses targeting the muscarinic 3 (M3 ) receptor gene into the bladder wall on bladder activity in rats with spinal cord injury (SCI). METHODS: Four M3 RNAi lentiviruses were constructed and used to infect primary cultured bladder smooth muscle cells (BSMCs). Western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were performed to determine the optimal RNAi lentivirus with the highest interference efficiency. Female Wistar rats were subjected spinal cord transection at T9-10 and randomly divided into three groups (n = 8), namely, blank control, negative control, and experimental groups, and injected into the bladder wall with saline, negative control shRNA, and M3 RNAi lentiviruses, respectively, 1 week after spinal cord transection. The normal rats were used as normal control group. Urodynamic parameters and bladder tissues were evaluated in the different groups. RESULTS: An M3 RNAi lentivirus with the highest interference efficiency (78.9%) was constructed and identified. Three weeks after injecting M3 RNAi lentiviruses into the bladder wall, Western blotting and qRT-PCR showed that the M3 receptor was significantly downregulated in the experimental group. Cystometric evaluation suggested that downregulating M3 receptor expression could substantially decrease basal pressure, residual volume, and non-voiding contraction number, increase intercontraction interval, and significantly improve bladder compliance in rats with SCI. CONCLUSION: Injecting RNAi lentiviruses targeting the M3 receptor gene into the bladder wall could effectively inhibit neurogenic detrusor overactivity (NDO) due to SCI. Thus, this approach may be a potential treatment for NDO in SCI.


Assuntos
Interferência de RNA , Receptores Muscarínicos/genética , Traumatismos da Medula Espinal/complicações , Bexiga Urinaria Neurogênica/terapia , Bexiga Urinária Hiperativa/terapia , Animais , Feminino , Lentivirus , Ratos , Ratos Wistar , Bexiga Urinaria Neurogênica/etiologia , Bexiga Urinária Hiperativa/etiologia , Urodinâmica/efeitos dos fármacos
18.
Int Urol Nephrol ; 51(1): 53-59, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30387068

RESUMO

PURPOSE: This study investigated the effect of gabapentin on lower urinary tract dysfunction focusing on urethral activities and cystitis-induced hyperalgesia in a mouse model of painful bladder syndrome/interstitial cystitis (PBS/IC). The electromyography (EMG) of external urethral sphincter (EUS) was difficult to obtain, but contained useful information to examine the drug effect in mice. METHODS: Female C57BL/6J mice were intraperitoneally (ip) administration with either saline or 200 mg/kg of cyclophosphamide (CYP) 48 h before experimental evaluation. Cystitis mice were treated with administration of gabapentin (25 or 50 mg/kg, ip). Cystometry and EUS EMG were obtained and analyzed during continuous bladder infusion. The visceral pain-related visceromotor reflex (VMR) was recorded in response to isotonic bladder distension. RESULTS: Cystitis mice showed shorter inter-contraction intervals and increased occurrence of non-voiding contractions during bladder infusion, with increased VMR during isotonic bladder distension, indicating cystitis-induced bladder hyperalgesia. Gabapentin (50 mg/kg) suppressed effects of CYP on cystometry, but not on EUS EMG activity, during bladder infusion. The effect on urodynamic recordings lasted 4 h. VMR was significantly reduced by gabapentin. CONCLUSIONS: The present study showed that CYP-induced cystitis in mice is a model of visceral hyperalgesia affecting detrusor contractions, not urethral activations. The technique of using EUS EMG to evaluate the drug effects on urethral activities is novel and useful for future investigations. Gabapentin can be as a potential treatment for detrusor overactivity and PBS/IC.


Assuntos
Cistite , Gabapentina/farmacologia , Hiperalgesia , Uretra , Analgésicos/farmacologia , Animais , Cistite/tratamento farmacológico , Cistite/fisiopatologia , Modelos Animais de Doenças , Eletromiografia/métodos , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Hiperalgesia/fisiopatologia , Camundongos , Contração Muscular/efeitos dos fármacos , Resultado do Tratamento , Uretra/efeitos dos fármacos , Uretra/fisiopatologia , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/fisiopatologia , Urodinâmica/efeitos dos fármacos
19.
Neurourol Urodyn ; 38(1): 97-106, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30411813

RESUMO

AIM: To investigate whether hyperbaric oxygen (HBO) is effective for the pathophysiological findings in an IC/PBS-like mouse model induced by intravesical hydrogen peroxide (H2 O2 ). METHODS: Six-week-old ICR female mice (N = 16) were divided into four experimental groups: (1) sham control with intravesical vehicle instillation twice, and without subsequent treatment (N = 4); (2) H2 O2 instillation twice, followed by HBO (100% O2 , 2 ATA, 30 min per session) (N = 4); (3) H2 O2 instillation twice, followed by dummy hyperbaric treatment (air, 2ATA, 30 min per session) (N = 4); and (4) H2 O2 instillation twice, followed by no treatment (N = 4). Body weight, voiding frequency, tidal voiding volume, and individual bladder pain threshold using the von-Frey test were measured. Whole body uptake of an inflammation-specific fluorescent pan-cathepsin was assessed by an in vivo imaging. Immunohistochemical staining and the mRNA expression of several biomarkers associated with chronic inflammation in resected bladders were evaluated. RESULTS: The HBO-treated group showed significant improvement in voiding frequency, tidal voiding volume, and the individual bladder pain threshold. Moreover, HBO markedly suppressed H2 O2 -induced inflammation, edema, and fibrosis in bladder wall, concomitant with a significant decrease in mRNA expressions of inflammation biomarkers and a significant increase in endothelial nitric oxide synthase expression. HBO also inhibited the expression of transient receptor potential channels induced by H2 O2 instillation. CONCLUSION: These results suggest that HBO contributes to elimination of H2 O2 -induced long-lasting cystitis through the repair of chronically inflamed bladder tissue and inhibition of the bladder sensory system.


Assuntos
Cistite/complicações , Cistite/terapia , Peróxido de Hidrogênio , Hiperalgesia/etiologia , Hiperalgesia/terapia , Oxigenação Hiperbárica , Oxidantes , Transtornos Urinários/etiologia , Transtornos Urinários/terapia , Administração Intravesical , Animais , Cistite/induzido quimicamente , Feminino , Peróxido de Hidrogênio/administração & dosagem , Inflamação/induzido quimicamente , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Limiar da Dor , Urodinâmica/efeitos dos fármacos
20.
Low Urin Tract Symptoms ; 11(2): O93-O97, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29697209

RESUMO

OBJECTIVE: We examined the efficacy and safety of mirabegron in elderly patients with urodynamic detrusor hyperactivity with impaired contractility (DHIC). METHODS: Patients diagnosed with DHIC received daily dose of mirabegron (25mg). Subjective symptom scores, uroflowmetry data, and adverse events (AEs) were recorded for all patients at baseline and after 1, 3, and 6 months treatment. Comparisons were made for each patient individually and between patients with detrusor overactivity (DO). RESULTS: Of the 65 patients enrolled in the study, 25 had DHIC and 40 had DO (mean [± SD] age 79.3 ± 9.6 and 75.6 ± 10.7 years, respectively). At the 6-month follow-up, significant (P < .05) improvement was seen compared with baseline in both the DHIC and DO groups in terms of OAB symptom scores (4.72 ± 3.05 vs. 6.88 ± 4.06 and 4.50 ± 2.99 vs. 6.70 ± 3.60, respectively), urgency severity score (1.90 ± 2.00 vs. 3.35 ± 1.13 and 1.58 ± 1.93 vs. 3.00 ± 1.65, respectively), and global response assessment (1.80 ± 1.41 and 1.73 ± 1.34, respectively). In the DHIC group, post-void residual (PVR) volume decreased from 153 ± 52.7 mL at baseline to 85.8 ± 90.1 mL at 6th month (P < .05) and voiding efficiency improved from 40.0 ± 20.7% to 62.6 ± 28.3% (P < .05). Common AEs included dry mouth and dizziness, yet 16% of DHIC patients developed PVR >180 mL. CONCLUSION: Mirabegron was an effective treatment option in elderly patients with urodynamic DO and DHIC in the present study. The AEs reported were mild and infrequent.


Assuntos
Acetanilidas/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 3/uso terapêutico , Tiazóis/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Acetanilidas/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 3/efeitos adversos , Idoso , Feminino , Humanos , Masculino , Tiazóis/efeitos adversos , Resultado do Tratamento , Urodinâmica/efeitos dos fármacos
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