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INTRODUCTION AND HYPOTHESIS: Female stress urinary incontinence (SUI) is a prevalent condition, and conservative treatment options are needed. Were evaluated CO2 laser and radiofrequency as treatment for SUI. METHODS: One hundred thirty-nine women with SUI were eligible and randomized in a three-arm double-blind randomized controlled trial into radiofrequency (RF), laser (LS) and sham control (SCT) groups, with 3-monthly outpatient treatment sessions. One hundred fourteen women were included, 38 in each group, during a 12-month follow-up. The primary outcomes were: subjective improvement of SUI, evaluated on a Likert scale, and objective cure, which was a composite outcome defined according to negative stress tests, voiding diary and pad test. Questionnaires were also applied. The sample size was calculated to provide 80% power to identify a 20% difference between groups, p < 0.05. RESULTS: Subjective improvement and objective cure of SUI were identified respectively in 72.6% and 45.2% in LS and in 61.7% and 44.7% in RF, both significantly higher than the 30.0% and 14.0% in SCT. Considering only mild cases (pad test < 10 g), objective cure was achieved in 66.7% in LS, 63.6% in RF and 22.2% in SCT. Significant reduction in the number of episodes of urinary incontinence was found according to voiding diaries (p = 0.029) and pad weight (p = 0.021). A significant reduction in urgency and urinary loss during sexual intercourse was observed only with LS and RF. Improvement in quality of life was also verified by the I-QoL and ICIQ-SF in favor of the energy-treated groups. CONCLUSIONS: CO2 laser and radiofrequency are outpatient options for SUI treatment, with no major complications. They had similar results and presented better results than in the sham control group.
Assuntos
Incontinência Urinária por Estresse , Incontinência Urinária , Feminino , Humanos , Incontinência Urinária por Estresse/cirurgia , Qualidade de Vida , Dióxido de Carbono , Grupos Controle , Resultado do TratamentoRESUMO
OBJECTIVE: To compare, in terms of anatomical, functional, and sexual aspects, two types of treatment for women with vaginal agenesis: progressive dilation or surgical neovaginoplasty. METHODS: Women with vaginal agenesis underwent either dilation treatment using the Frank method or surgical treatment using the modified Abbé-McIndoe technique with oxidized cellulose. Patients were evaluated 3-6 months after treatment for a follow-up including medical history, physical examination, general satisfaction, clinical aspect of the vagina, Female Sexual Function Index, and three-dimensional pelvic floor ultrasound. RESULTS: In total, 20 women with vaginal agenesis were included in the present study; nine in the dilation group and 11 in the surgical group. A comparison between the groups (vaginal dilation and surgical neovaginoplasty) showed efficacy in neovagina formation after both treatments, with a statistically significant difference between the pre- and post-treatment periods (P value pre- × post-dilation group <0.0001 and P value pre- × post-surgical group <0.0001). There were no statistical differences in total vaginal length measurements (P value post-dilation × post-surgical = 0.09) or Female Sexual Function Index scores (P = 0.72) after both treatments. CONCLUSION: Both treatments had satisfactory efficacy and positive outcomes for patients with vaginal agenesis concerning anatomical, functional, and sexual aspects, with minimum complications in the surgical group. Dilation treatment can remain the first-line therapy.
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Transtornos 46, XX do Desenvolvimento Sexual , Anormalidades Congênitas , Procedimentos de Cirurgia Plástica , Transtornos 46, XX do Desenvolvimento Sexual/cirurgia , Anormalidades Congênitas/cirurgia , Dilatação/efeitos adversos , Dilatação/métodos , Feminino , Procedimentos Cirúrgicos em Ginecologia/métodos , Humanos , Masculino , Ductos Paramesonéfricos/anormalidades , Ductos Paramesonéfricos/cirurgia , Estudos Prospectivos , Procedimentos de Cirurgia Plástica/efeitos adversos , Resultado do Tratamento , Vagina/anormalidadesRESUMO
Most approved vaccines against COVID-19 have to be administered in a prime/boost regimen. We engineered a novel vaccine based on a chimeric human adenovirus 5 (hAdV5) vector. The vaccine (named CoroVaxG.3) is based on three pillars: (i) high expression of Spike to enhance its immunodominance by using a potent promoter and an mRNA stabilizer; (ii) enhanced infection of muscle and dendritic cells by replacing the fiber knob domain of hAdV5 by hAdV3; (iii) use of Spike stabilized in a prefusion conformation. The transduction with CoroVaxG.3-expressing Spike (D614G) dramatically enhanced the Spike expression in human muscle cells, monocytes and dendritic cells compared to CoroVaxG.5 that expressed the native fiber knob domain. A single dose of CoroVaxG.3 induced a potent humoral immunity with a balanced Th1/Th2 ratio and potent T-cell immunity, both lasting for at least 5 months. Sera from CoroVaxG.3-vaccinated mice was able to neutralize pseudoviruses expressing B.1 (wild type D614G), B.1.117 (alpha), P.1 (gamma) and B.1.617.2 (delta) Spikes, as well as an authentic P.1 SARS-CoV-2 isolate. Neutralizing antibodies did not wane even after 5 months, making this kind of vaccine a likely candidate to enter clinical trials.
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AIMS: To verify if hypopressive exercises (HEs) can improve pelvic organ prolapse (POP) symptoms equally or better than pelvic floor muscle training (PFMT). METHODS: Randomized controlled trial. Symptomatic women with untreated stage II POP according to the Pelvic Organ Prolapse Quantification System (POP-Q) having the ability to contract their pelvic floor muscles were invited. The outcome measures were POP symptoms as measured by specific questions and Prolapse Quality of Life (P-QoL); POP severity as measured by POP-Q; and PFM function. Intervention consisted by 12 weeks of PFMT or an HE home exercise program with bimonthly sessions with a physiotherapist. The protocol consisted of three initial sessions to learn how to perform the exercises correctly, followed by 3 months of exercise with monthly progression. Volunteers filled out exercise diaries to record their compliance. RESULTS: PFMT presented better results in terms of the following symptoms: a bulge/lump from or in the vagina, heaviness or dragging on the lower abdomen, and stress incontinence. PFMT also presented better results regarding the Prolapse impact and role, social and personal limitations of P-QoL. Regarding the total number of symptoms at the end, the PFMT group presented a mean of 1.7 (±1.2), and the HE group presented a mean of 2.8 (±1,1); the effect size was 1.01 in favor of the PFMT group (95%CI = 1.002-1.021). CONCLUSION: Both groups exhibited improvements in POP symptoms, quality of life, prolapse severity, and PFM function. PFMT was superior to HE for all outcomes.
Assuntos
Terapia por Exercício/métodos , Diafragma da Pelve , Prolapso de Órgão Pélvico/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Prolapso de Órgão Pélvico/psicologia , Qualidade de Vida , Resultado do Tratamento , Incontinência Urinária por Estresse/etiologia , Incontinência Urinária por Estresse/terapiaRESUMO
INTRODUCTION AND HYPOTHESIS: Double Incontinence (DI) is incontinence of urine and stool and is an extreme manifestation of pelvic floor dysfunction. The objective of this study was to estimate the prevalence and incidence of DI and the risk factors in elderly women in São Paulo, Brazil. METHODS: This was a prospective study in women aged 65 years or older evaluated in 2006 and re-evaluated in 2010. The sample was selected by two-phase stratified sampling with replacement and probability proportional to size. The likelihood ratio test was performed and Cox regression curves were generated to evaluate the equality of survival. Poisson's regression was used to evaluate risk factors. RESULTS: This is the first study on the incidence of DI in elderly women. A total of 864 elderly women were interviewed in 2006. The prevalence rate of DI was 4.9%. The incidence rate of DI in the period between 2006 and 2010 was 13.8/1,000 person-years. Associated factors were the presence of chronic obstructive pulmonary disease, hypertension, difficulty with basic activities of daily living (BADL) and instrumental activities of daily living (IADL), polypharmacy and falls in the last year. Poisson's regression analysis showed that falls in the last year and difficulty with at least three IADL were risk factors for DI. CONCLUSIONS: The incidence of DI seems to be high in this population. Falls in the last year and difficulty with at least three IADL were identified as risk factors. Preventive measures must be implemented with public health policies to prevent increases in DI.
Assuntos
Incontinência Fecal/epidemiologia , Distúrbios do Assoalho Pélvico/complicações , Incontinência Urinária/epidemiologia , Atividades Cotidianas , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Incontinência Fecal/etiologia , Feminino , Avaliação Geriátrica , Humanos , Incidência , Distribuição de Poisson , Prevalência , Modelos de Riscos Proporcionais , Análise de Regressão , Fatores de Risco , Incontinência Urinária/etiologiaRESUMO
Abstract Objective Using three-dimensional ultrasound (3D-US), we aimed to compare the tape position and the angle formed by the sling arms in different techniques of midurethral sling insertion for the surgical treatment of stress urinary incontinence, three years after surgery. In addition, we examined the correlations between the US findings and the clinical late postoperative results. Methods A prospective cross-sectional cohort study of 170 patients who underwent a sling procedure between May 2009 and December 2011 was performed. The final sample, with US images of sufficient quality, included 26 retropubic slings (tension-free vaginal tape, TVT), 42 transobturator slings (tension-free vaginal tape-obturator, TVTO), and 37 single-incision slings (tension-free vaginal tape-Secur, TVT-S). The images (at rest, during the Valsalva maneuver, and during pelvic floor contraction) were analyzed offline by 2 different observers blinded against the surgical and urinary continence status. Group comparisons were performed using the Student t-test, the chi-squared and the Kruskal-Wallis tests, and analyses of variance with Tukey multiple comparisons. Results Differences among the groups were found in themean angle of the tape arms (TVT = 119.94°, TVT-O = 141.93°, TVT-S = 121.06°; p < 0.001) and in the distance between the bladder neck and the tape at rest (TVT = 1.65 cm, TVT-O = 1.93 cm, TVTS = 1.95 cm; p = 0.010). The global objective cure rate was of 87.8% (TVT = 88.5%, TVT-O = 90.5%, TVT-S = 83.8%; p = 0.701). The overall subjective cure rate was of 83.8% (TVT = 88.5%, TVT-O = 88.5% and TVT-S = 78.4%; p = 0.514). The slings were located in the mid-urethra in 85.7% of the patients (TVT = 100%, TVT-O = 73.8%, TVTS = 89.2%; p = 0.001), with a more distal location associated with obesity (distal: 66.7% obese; mid-urethra: 34% obese; p = 0.003). Urgency-related symptoms were observed in 23.8% of the patients (TVT = 30.8%, TVT-O = 21.4%, TVT-S = 21.6%; p = 0.630). Conclusions The angle formed by the arms of the sling tape was more obtuse for the transobturator slings compared with the angles for the retropubic or single-incision slings. Retropubic slings were more frequently located in the mid-urethra compared with the other slings, regardless of obesity. However, the analyzed sonographic measures did not correlate with the urinary symptoms three years after the surgery.
Resumo Objetivo Comparar por meio de ultrassom tridimensional (US-3D) a posição e o ângulo entre os braços da faixa, em diferentes técnicas de inserção de sling de uretra média, para tratamento de incontinência urinária de esforço, 3 anos após a cirurgia, correlacionando os achados ultrassonográficos aos resultados clínicos pós-operatórios. Métodos Este é umestudo de coorte transversal prospectivo de 170 pacientes que se submeteram a um procedimento de sling entremaio de 2009 e dezembro de 2011. Foi possível avaliar as imagens de US em 105 pacientes: 26 com tension-free vaginal tape (TVT), 42 com tension-free vaginal tape-obturator (TVT-O) e 37 com tension-free vaginal tape-Secur (TVT-S). As imagens (em repouso, em manobra de Valsalva e em contração perineal) foram analisadas por dois observadores diferentes, que desconheciam o tipo de sling utilizado na cirurgia, assimcomo as queixas da paciente. A análise estatística foi realizada por meio dos testes t de Student, qui-quadrado, Kruskal-Wallis, e análise de variância com comparações múltiplas de Tukey. Resultados As médias dos ângulos entre os braços da faixa foram: TVT = 119,94°, TVT-O = 141,93°, TVT-S = 121,06° (p < 0,001). As médias das distâncias entre o colo vesical e a faixa, em repouso, foram: TVT = 1,65 cm, TVT-O = 1,93 cm, TVTS = 1,95 cm (p = 0,010). A taxa de cura objetiva dos slings foi de 87,8% (TVT = 88,5%, TVT-O = 90,5% e TVT-S = 83,8%; p = 0,701). A taxa de cura subjetiva foi de 83,8% (TVT = 88,5%, TVT-O = 88,5% e TVT-S = 78,4%; p = 0,514). Os slings estavam na uretra média em 85,7% (TVT = 100%, TVT-O = 73,8% e TVT-S = 89,2%; p = 0,001) dos pacientes, e a localização mais distal foi associada a obesidade (distal: 66,7% obesas; uretra média: 34% obesas; p = 0.003). Os sintomas de urgência foram observados em 23,8% das pacientes (TVT = 30,8%, TVT-O = 21,4%, TVT-S = 21,6%; p = 0,630). Não houve diferenças significativas quando se comparam os achados ultrassonográficos e os grupos de pacientes com sintomas de urgência, cura subjetiva e objetiva. Conclusão O ângulo formado pelos braços da faixa foi mais obtuso noTVT-Oquando comparado com o TVT ou o TVT-S. Os TVTs foram localizados mais frequentemente na uretra média quando comparados com os outros dois grupos, mesmo em pacientes obesas. Entretanto, as medidas ultrassonográficas não tiveram correlação com os sintomas urinários três anos após a cirurgia.
Assuntos
Humanos , Feminino , Incontinência Urinária por Estresse/cirurgia , Incontinência Urinária por Estresse/diagnóstico por imagem , Diafragma da Pelve/diagnóstico por imagem , Imageamento Tridimensional , Slings Suburetrais , Fatores de Tempo , Estudos Transversais , Estudos Prospectivos , Seguimentos , Ultrassonografia , Pessoa de Meia-IdadeRESUMO
Objective Using three-dimensional ultrasound (3D-US), we aimed to compare the tape position and the angle formed by the sling arms in different techniques of mid-urethral sling insertion for the surgical treatment of stress urinary incontinence, three years after surgery. In addition, we examined the correlations between the US findings and the clinical late postoperative results. Methods A prospective cross-sectional cohort study of 170 patients who underwent a sling procedure between May 2009 and December 2011 was performed. The final sample, with US images of sufficient quality, included 26 retropubic slings (tension-free vaginal tape, TVT), 42 transobturator slings (tension-free vaginal tape-obturator, TVT-O), and 37 single-incision slings (tension-free vaginal tape-Secur, TVT-S). The images (at rest, during the Valsalva maneuver, and during pelvic floor contraction) were analyzed offline by 2 different observers blinded against the surgical and urinary continence status. Group comparisons were performed using the Student t-test, the chi-squared and the Kruskal-Wallis tests, and analyses of variance with Tukey multiple comparisons. Results Differences among the groups were found in the mean angle of the tape arms (TVT = 119.94°, TVT-O = 141.93°, TVT-S = 121.06°; p < 0.001) and in the distance between the bladder neck and the tape at rest (TVT = 1.65 cm, TVT-O = 1.93 cm, TVT-S = 1.95 cm; p = 0.010). The global objective cure rate was of 87.8% (TVT = 88.5%, TVT-O = 90.5%, TVT-S = 83.8%; p = 0.701). The overall subjective cure rate was of 83.8% (TVT = 88.5%, TVT-O = 88.5% and TVT-S = 78.4%; p = 0.514). The slings were located in the mid-urethra in 85.7% of the patients (TVT = 100%, TVT-O = 73.8%, TVT-S = 89.2%; p = 0.001), with a more distal location associated with obesity (distal: 66.7% obese; mid-urethra: 34% obese; p = 0.003). Urgency-related symptoms were observed in 23.8% of the patients (TVT = 30.8%, TVT-O = 21.4%, TVT-S = 21.6%; p = 0.630). Conclusions The angle formed by the arms of the sling tape was more obtuse for the transobturator slings compared with the angles for the retropubic or single-incision slings. Retropubic slings were more frequently located in the mid-urethra compared with the other slings, regardless of obesity. However, the analyzed sonographic measures did not correlate with the urinary symptoms three years after the surgery.
Objetivo Comparar por meio de ultrassom tridimensional (US-3D) a posição e o ângulo entre os braços da faixa, em diferentes técnicas de inserção de sling de uretra média, para tratamento de incontinência urinária de esforço, 3 anos após a cirurgia, correlacionando os achados ultrassonográficos aos resultados clínicos pós-operatórios. Métodos Este é um estudo de coorte transversal prospectivo de 170 pacientes que se submeteram a um procedimento de sling entre maio de 2009 e dezembro de 2011. Foi possível avaliar as imagens de US em 105 pacientes: 26 com tension-free vaginal tape (TVT), 42 com tension-free vaginal tape-obturator (TVT-O) e 37 com tension-free vaginal tape-Secur (TVT-S). As imagens (em repouso, em manobra de Valsalva e em contração perineal) foram analisadas por dois observadores diferentes, que desconheciam o tipo de sling utilizado na cirurgia, assim como as queixas da paciente. A análise estatística foi realizada por meio dos testes t de Student, qui-quadrado, Kruskal-Wallis, e análise de variância com comparações múltiplas de Tukey. Resultados As médias dos ângulos entre os braços da faixa foram: TVT = 119,94°, TVT-O = 141,93°, TVT-S = 121,06° (p < 0,001). As médias das distâncias entre o colo vesical e a faixa, em repouso, foram: TVT = 1,65 cm, TVT-O = 1,93 cm, TVT-S = 1,95 cm (p = 0,010). A taxa de cura objetiva dos slings foi de 87,8% (TVT = 88,5%, TVT-O = 90,5% e TVT-S = 83,8%; p = 0,701). A taxa de cura subjetiva foi de 83,8% (TVT = 88,5%, TVT-O = 88,5% e TVT-S = 78,4%; p = 0,514). Os slings estavam na uretra média em 85,7% (TVT = 100%, TVT-O = 73,8% e TVT-S = 89,2%; p = 0,001) dos pacientes, e a localização mais distal foi associada a obesidade (distal: 66,7% obesas; uretra média: 34% obesas; p = 0.003). Os sintomas de urgência foram observados em 23,8% das pacientes (TVT = 30,8%, TVT-O = 21,4%, TVT-S = 21,6%; p = 0,630). Não houve diferenças significativas quando se comparam os achados ultrassonográficos e os grupos de pacientes com sintomas de urgência, cura subjetiva e objetiva. Conclusão O ângulo formado pelos braços da faixa foi mais obtuso no TVT-O quando comparado com o TVT ou o TVT-S. Os TVTs foram localizados mais frequentemente na uretra média quando comparados com os outros dois grupos, mesmo em pacientes obesas. Entretanto, as medidas ultrassonográficas não tiveram correlação com os sintomas urinários três anos após a cirurgia.
Assuntos
Imageamento Tridimensional , Diafragma da Pelve/diagnóstico por imagem , Slings Suburetrais , Incontinência Urinária por Estresse/diagnóstico por imagem , Incontinência Urinária por Estresse/cirurgia , Estudos Transversais , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , UltrassonografiaRESUMO
INTRODUCTION AND HYPOTHESIS: The efficacy and safety of removing or preserving the uterus during reconstructive pelvic surgery is a matter of debate. METHODS: We performed a systematic review and meta-analysis of studies that compared hysteropreservation and hysterectomy in the management of uterine prolapse. PubMed, Medline, SciELO and LILACS databases were searched from inception until January 2017. We selected only randomized controlled trials and observational cohort prospective comparative studies. Primary outcomes were recurrence and reoperation rates. Secondary outcomes were: operative time, blood loss, visceral injury, voiding dysfunction, duration of catheterization, length of hospital stay, mesh exposure, dyspareunia, malignant neoplasia and quality of life. RESULTS: Eleven studies (six randomized and five non-randomized) were included involving 910 patients (462 in the hysteropreservation group and 448 in the hysterectomy group). Pooled data including all surgical techniques showed no difference between the groups regarding recurrence of uterine prolapse (RR 1.65, 95% CI 0.88-3.10; p = 0.12), but the risk of recurrence following hysterectomy was lower when the vaginal route was used with native tissue repair (RR 10.61; 95% CI 1.26-88.94; p = 0.03). Hysterectomy was associated with a lower reoperation rate for any prolapse compartment than hysteropreservation (RR 2.05; 95% CI 1.13-3.74; p = 0.02). Hysteropreservation was associated with a shorter operative time (mean difference -12.43 min; 95% CI -14.11 to -10.74 ; p < 0.00001) and less blood loss (mean difference -60.42 ml; 95% CI -71.31 to -49.53 ml; p < 0.00001). Other variables were similar between the groups. CONCLUSIONS: Overall, the rate of recurrence of uterine prolapse was not lower but the rate of reoperation for prolapse was lower following hysterectomy, while operative time was shorter and blood loss was less with hysteropreservation. The limitations of this analysis were the inclusion of nonrandomized studies and the variety of surgical techniques. The results should be interpreted with caution due to potential biases.
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Histerectomia , Tratamentos com Preservação do Órgão , Prolapso Uterino/cirurgia , Feminino , HumanosRESUMO
Human plasma kallikrein (huPK) potentiates platelet responses to subthreshold doses of ADP, although huPK itself, does not induce platelet aggregation. In the present investigation, we observe that huPK pretreatment of platelets potentiates ADP-induced platelet activation by prior proteolysis of the G-protein-coupled receptor PAR-1. The potentiation of ADP-induced platelet activation by huPK is mediated by the integrin αIIbß3 through interactions with the KGD/KGE sequence motif in huPK. Integrin αIIbß3 is a cofactor for huPK binding to platelets to support PAR-1 hydrolysis that contributes to activation of the ADP signaling pathway. This activation pathway leads to phosphorylation of Src, AktS473, ERK1/2, and p38 MAPK, and to Ca2+ release. The effect of huPK is blocked by specific antagonists of PAR-1 (SCH 19197) and αIIbß3 (abciximab) and by synthetic peptides comprising the KGD and KGE sequence motifs of huPK. Further, recombinant plasma kallikrein inhibitor, rBbKI, also blocks this entire mechanism. These results suggest a new function for huPK. Formation of plasma kallikrein lowers the threshold for ADP-induced platelet activation. The present observations are consistent with the notion that plasma kallikrein promotes vascular disease and thrombosis in the intravascular compartment and its inhibition may ameliorate cardiovascular disease and thrombosis.
Assuntos
Difosfato de Adenosina/farmacologia , Calicreína Plasmática/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Humanos , Fosforilação/efeitos dos fármacos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Receptor PAR-1/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Cell culture is considered the standard media used in research to emulate the in vivo cell environment. Crucial in vivo experiments cannot be conducted in humans and depend on in vitro methodologies such as cell culture systems. However, some procedures involving the quality control of cells in culture have been gradually neglected by failing to acknowledge that primary cells and cell lines change over time in culture. Thus, we report methods based on our experience for monitoring primary cell culture of human myometrial cells derived from uterine leiomyoma. We standardized the best procedure of tissue dissociation required for the study of multiple genetic marker systems that include species-specific antigens, expression of myofibroblast or myoblast markers, growth curve, serum deprivation, starvation by cell cycle synchronization, culture on collagen coated plates, and 17 ß-estradiol (E2) and progesterone (P4) effects. The results showed that primary myometrial cells from patients with uterine leiomyoma displayed myoblast phenotypes before and after in vitro cultivation, and leiomyoma cells differentiated into mature myocyte cells under the appropriate differentiation-inducing conditions (serum deprivation). These cells grew well on collagen coated plates and responded to E2 and P4, which may drive myometrial and leiomyoma cells to proliferate and adhere into a focal adhesion complex involvement in a paracrine manner. The establishment of these techniques as routine procedures will improve the understanding of the myometrial physiology and pathogenesis of myometrium-derived diseases such as leiomyoma. Mimicking the in vivo environment of fibrotic conditions can prevent false results and enhance results that are based on cell culture integrity.
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Leiomioma/patologia , Miométrio/citologia , Neoplasias Uterinas/patologia , Adulto , Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Estradiol/farmacologia , Feminino , Citometria de Fluxo , Humanos , Leiomioma/metabolismo , Masculino , Microscopia de Fluorescência , Mycoplasma/citologia , Mycoplasma/metabolismo , Miométrio/metabolismo , Fosfoproteínas/metabolismo , Progesterona/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Neoplasias Uterinas/metabolismoRESUMO
BACKGROUND: Breast cancer comprises clinically and molecularly distinct tumor subgroups that differ in cell histology and biology and show divergent clinical phenotypes that impede phase III trials, such as those utilizing cathepsin K inhibitors. Here we correlate the epithelial-mesenchymal-like transition breast cancer cells and cathepsin K secretion with activation and aggregation of platelets. Cathepsin K is up-regulated in cancer cells that proteolyze extracellular matrix and contributes to invasiveness. Although proteolytically activated receptors (PARs) are activated by proteases, the direct interaction of cysteine cathepsins with PARs is poorly understood. In human platelets, PAR-1 and -4 are highly expressed, but PAR-3 shows low expression and unclear functions. METHODS: Platelet aggregation was monitored by measuring changes in turbidity. Platelets were immunoblotted with anti-phospho and total p38, Src-Tyr-416, FAK-Tyr-397, and TGFß monoclonal antibody. Activation was measured in a flow cytometer and calcium mobilization in a confocal microscope. Mammary epithelial cells were prepared from the primary breast cancer samples of 15 women with Luminal-B subtype to produce primary cells. RESULTS: We demonstrate that platelets are aggregated by cathepsin K in a dose-dependent manner, but not by other cysteine cathepsins. PARs-3 and -4 were confirmed as the cathepsin K target by immunodetection and specific antagonists using a fibroblast cell line derived from PARs deficient mice. Moreover, through co-culture experiments, we show that platelets activated by cathepsin K mediated the up-regulation of SHH, PTHrP, OPN, and TGFß in epithelial-mesenchymal-like cells from patients with Luminal B breast cancer. CONCLUSIONS: Cathepsin K induces platelet dysfunction and affects signaling in breast cancer cells.
Assuntos
Plaquetas/metabolismo , Neoplasias da Mama/metabolismo , Catepsina K/metabolismo , Transdução de Sinais , Proteínas Adaptadoras de Transdução de Sinal , Animais , Plaquetas/efeitos dos fármacos , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Cálcio/metabolismo , Catepsina K/farmacologia , Proteínas de Ciclo Celular/antagonistas & inibidores , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Feminino , Proteínas Hedgehog/metabolismo , Humanos , Hidrólise , Ligantes , Proteínas de Membrana/antagonistas & inibidores , Camundongos , Fosforilação , Ativação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Proteólise , Receptores de Trombina/antagonistas & inibidores , Trombina/metabolismo , Trombina/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Quinases da Família src/metabolismoRESUMO
Endometriosis affects approximately 12% of reproductive-age women and is currently diagnosed using invasive laparoscopic surgery. Differences in gene expression in the eutopic endometrium between women with and without endometriosis have been reported, and determining the reproducibility of these genetic differences in the endocervical epithelium would represent an important step toward developing novel diagnostic strategies. In this study, we analyzed gene expression in the endocervical epithelium in women with and without moderate or severe endometriosis. Using RT2 Profiler PCR Arrays, we analyzed gene expression in endocervical epithelial cells from women with deep endometriosis (n = 4) and healthy women (n =6). Nine genes were identified as being upregulated: 5 cell cycle genes (cyclin B1 [CCNB1], cyclin G1 [CCNG1], cullin 1 [CUL1], general transcription factor IIH, polypeptide 1 [GTF2H1], and proliferating cell nuclear antigen [PCNA]), 3 cytokine genes (C3, chemokine (C-C motif) ligand 21 [CCL21], and chemokine (C-X-C motif) ligand 14 [CXCL14]) and 1 gene related to dendritic cell pathways (ICAM2), showing that differential gene expression is present in the endocervical epithelium of women with deep endometriosis.
Assuntos
Endometriose/genética , Endometriose/metabolismo , Expressão Gênica , Útero/metabolismo , Adulto , Células Epiteliais/metabolismo , Feminino , Perfilação da Expressão Gênica , HumanosRESUMO
AIMS: To compare efficacy and safety of the traditional colporraphy and transvaginal polypropylene mesh for the treatment of advanced anterior vaginal prolapse according to different success criteria in two-year follow-up. METHODS: In this randomized controlled trial, women with anterior prolapse stage II or greater, with Ba point ≥ +1 (POP-Q quantification), were randomly assigned to have either anterior colporraphy (n = 43) or transvaginal mesh repair (n = 43). The primary outcome was to compare objective success rate under two success definitions: prolapse stage I (Ba < -1) and stage II (Ba < 0). Secondary outcomes included complications and prolapse symptoms, satisfaction and quality of life (QoL). Intention to treat was used for the primary endpoint and per protocol analysis for the secondary outcomes. RESULTS: The groups presented similar preoperative data. Thirty three patients from the colporraphy and 37 from the mesh groups completed two-year follow-up. Under Ba < -1 definition, success rate was 39.53% for both groups (P = 1.00). Considering success as Ba < 0, analysis favored the mesh group by 23% (51.16% and 74.42%; 95% CI for difference: 3-43%; P = 0.022). Patients from the mesh group were more satisfied after two years (81.8% and 97.3% for colporraphy and mesh, respectively, 15.5% difference; 95% CI for difference 1-29%; P = 0.032). Both procedures similarly improved women's symptoms and QoL. Some complications were observed, one being a 13.5% mesh exposure rate. CONCLUSIONS: Transvaginal synthetic mesh repair for advanced anterior vaginal prolapse provided higher anatomical success and satisfaction rates compared with traditional colporraphy. Both procedures equally improved quality of life. Neurourol. Urodynam. 35:509-514, 2016. © 2015 Wiley Periodicals, Inc.
Assuntos
Procedimentos de Cirurgia Plástica/métodos , Telas Cirúrgicas , Prolapso Uterino/cirurgia , Vagina/cirurgia , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Satisfação do Paciente , Períneo/cirurgia , Qualidade de Vida , Resultado do TratamentoRESUMO
AIM OF THE VIDEO / INTRODUCTION: Pelvic congestion syndrome is a well-known cause of cyclic pelvic pain (Ganeshan et al., Cardiovasc Intervent Radiol 30(6):1105-11, 2007). What is much less well known is that dilated or malformed branches of the internal or external iliac vessels can entrap the nerves of the sacral plexus against the pelvic sidewalls, producing symptoms that are not commonly seen in gynecological practice, such as sciatica, or refractory urinary and anorectal dysfunction (Possover et al., Fertil Steril 95(2):756-8. 2011). The objective of this video is to explain and describe the symptoms suggestive of vascular entrapment of the sacral plexus, as well as the technique for the laparoscopic decompression of these nerves. METHOD: Two anecdotal cases of intrapelvic vascular entrapment are used to review the anatomy of the lumbosacral plexus and demonstrate the laparoscopic surgical technique for decompression at two different sites, one on the sciatic nerve and one on the sacral nerve roots. RESULT: After surgery, the patient with the sciatic entrapment showed full recovery of the sciatica and partial recovery of the myofascial pain. The patient with sacral nerve root entrapment showed full recovery with resolution of symptoms. CONCLUSION: The symptoms suggestive of intrapelvic nerve entrapment are: perineal pain or pain irradiating to the lower limbs in the absence of a spinal disorder, and lower urinary tract symptoms in the absence of prolapse of a bladder lesion. In the presence of such symptoms, the radiologist should provide specific MRI sequences of the intrapelvic portion of the sacral plexus and a team and equipment to expose and decompress the sacral nerves should be prepared.
Assuntos
Endometriose/complicações , Síndromes de Compressão Nervosa/etiologia , Nervo Isquiático , Doenças do Colo Sigmoide/complicações , Malformações Vasculares/complicações , Adulto , Endometriose/cirurgia , Feminino , Humanos , Ligamentos/patologia , Ligamentos/cirurgia , Sintomas do Trato Urinário Inferior/etiologia , Síndromes de Compressão Nervosa/cirurgia , Ciática/etiologia , Doenças do Colo Sigmoide/cirurgia , Malformações Vasculares/cirurgia , Veias/anormalidades , Veias/cirurgiaRESUMO
INTRODUCTION AND HYPOTHESIS: The laparoscopic implantation of neuromodulation electrodes--the LION procedure--was first described as a rescue procedure in patients with local complications of a Brindley procedure. The objective of this video article is to demonstrate the technique for the laparoscopic implantation of electrodes for bilateral neuromodulation of femoral, sciatic and pudendal nerves and describe our initial experience with two multiple sclerosis (MS) patients. METHOD: This is a retrospective analysis of two patients with MS and neurogenic detrusor overactivity. A quadripolar electrode was implanted with two poles into the Alcock's canal and the two other laying over the lumbosacral trunk. The other two electrodes were implanted posteriorly to the femoral nerves. RESULTS: At the neuromodulation trial, both patients presented a full recovery of urinary symptoms. One of them found it easier to stand up for transfers and daily activities and the other managed to advance from the wheelchair to the walker and both patients received the permanent implant. At 1-year follow up, urinary results were maintained and 1 patient presented a disease relapse, demanding multiple reprogramming sessions. CONCLUSION: Our initial observations are encouraging and indicate that the LION procedure seems to produce in MS patients similar results to those observed in patients with spinal cord injury. Patients, however, should be advised that MS is a progressive disease and that the positive effects of neuromodulation can potentially fade with time and that multiple reprogramming sessions might be necessary.
Assuntos
Terapia por Estimulação Elétrica , Eletrodos Implantados , Laparoscopia , Esclerose Múltipla/complicações , Esclerose Múltipla/terapia , Incontinência Urinária/terapia , Adulto , Feminino , Humanos , Locomoção , Pessoa de Meia-Idade , Esclerose Múltipla/fisiopatologia , Resultado do Tratamento , Incontinência Urinária/etiologia , Incontinência Urinária/fisiopatologiaRESUMO
OBJECTIVE: To determine the efficacy and safety of a single-incision mini-sling compared with a transobturator midurethral sling for stress urinary incontinence (SUI) treatment. METHODS: This prospective single-center randomized controlled trial involved 130 women with a diagnosis of SUI. Primary outcomes were the objective and subjective cure rates, defined as negative cough stress and pad tests, and satisfaction rates. Quality of life assessed by the Incontinence Quality of Life Questionnaire and the Urogenital Distress Inventory Short Form, operation time, complications, and reoperation rates were also recorded. The efficacy was analyzed using a noninferiority test with a margin of 15%. For the noninferiority test, a P value >.05 rejects the noninferiority hypothesis of the mini-sling. RESULTS: Sixty-four patients in the mini-sling group and 56 in the transobturator group completed the 12-month follow-up. The objective cure rates for the mini-sling and the transobturator sling were 68.1% and 81.9% (absolute difference 13.8; 90% confidence interval [CI] 1.5-26.1; P=.439) and the subjective cure rates were 81.1% and 88.5% (absolute difference 7.4%; 90% CI 2.8-17.6; P=.110), respectively. There was a significant improvement in quality of life in both groups. Thigh pain was greater after the transobturator sling, four patients (7.1%) compared with zero (P=.045). The mean operation time was 5 minutes shorter for the mini-sling procedure (P=.000). Five patients (7.8%) in the mini-sling group and one patient (1.8%) in the transobturator group underwent surgical reintervention for persistent SUI (P=.213). CONCLUSION: The noninferiority of the mini-sling could not be demonstrated in this study at the 12-month follow-up. The mini-sling was associated with shorter operative time and less postoperative thigh pain. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01094353.