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1.
J Endocr Soc ; 3(11): 2123-2134, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31687639

RESUMO

Müllerian-inhibiting substance (MIS), also known as anti-Müllerian hormone, is thought to be a negative regulator of primordial follicle activation. We have previously reported that treatment with exogenous MIS can induce complete ovarian suppression within 5 weeks of treatment in mice. To investigate the kinetics of the return of folliculogenesis following the reversal of suppression, we treated animals with recombinant human MIS (rhMIS) protein for 40 days in adult female Nu/Nu mice and monitored the recovery of each follicle type over time. Following cessation of MIS therapy, secondary, and antral follicles returned within 30 days, along with the normalization of reproductive hormones, including LH, FSH, MIS, and Inhibin B. Furthermore, 30 days following MIS pretreatment, the number of antral follicles were significantly higher than controls, and superovulation with timed pregnant mare serum gonadotropin and human chorionic gonadotropin stimulation at this time point resulted in an approximately threefold increased yield of eggs. Use of the combined rhMIS-gonadotropin superovulation regimen in a diminished ovarian reserve (DOR) mouse model, created by 4-vinylcyclohexene dioxide treatment, also resulted in a twofold improvement in the yield of eggs. In conclusion, treatment with rhMIS can induce a reversible ovarian suppression, following which a rapid and synchronized large initial wave of growing follicles can be harnessed to enhance the response to superovulation. Therapies modulating MIS signaling may therefore augment the response to current ovarian stimulation protocols and could be particularly useful to women with DOR or poor responders to controlled ovarian hyperstimulation during in vitro fertilization.

2.
Elife ; 82019 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-31232694

RESUMO

The Mullerian ducts are the anlagen of the female reproductive tract, which regress in the male fetus in response to MIS. This process is driven by subluminal mesenchymal cells expressing Misr2, which trigger the regression of the adjacent Mullerian ductal epithelium. In females, these Misr2+ cells are retained, yet their contribution to the development of the uterus remains unknown. Here, we report that subluminal Misr2+ cells persist postnatally in the uterus of rodents, but recede by week 37 of gestation in humans. Using single-cell RNA sequencing, we demonstrate that ectopic postnatal MIS administration inhibits these cells and prevents the formation of endometrial stroma in rodents, suggesting a progenitor function. Exposure to MIS during the first six days of life, by inhibiting specification of the stroma, dysregulates paracrine signals necessary for uterine development, eventually resulting in apoptosis of the Misr2+ cells, uterine hypoplasia, and complete infertility in the adult female.

3.
J Laparoendosc Adv Surg Tech A ; 29(4): 573-578, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30614751

RESUMO

Extrahepatic congenital portosystemic shunts (CPSSs) can be occluded by surgical or endovascular approaches. However, when the estimated portal vein (PV) pressure after the closure is high enough to induce symptoms associated with portal hypertension, partial closure is recommended to avoid life-threatening events. In this study, we attempted laparoscopic partial closure of a CPSS in two patients. Along with intraoperative real-time measuring of the PV pressure and angiography, laparoscopic partial closure was performed to achieve a PV pressure of ≤25 mmHg. Subsequently, the intrahepatic portal system grew in both patients. The partially ligated CPSS closed spontaneously in the first patient. In the second patient, laparoscopic complete closure was performed for the residual CPSS 6 months after the first operation. To our knowledge, this is the first report of laparoscopic partial closure for CPSS. Minimally invasive laparoscopic partial ligation of CPSS is technically feasible and useful when the estimated PV pressure is too high to tolerate one-step complete closure.


Assuntos
Hipertensão Portal/cirurgia , Laparoscopia/métodos , Veia Porta/anormalidades , Veia Porta/cirurgia , Malformações Vasculares/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Pré-Escolar , Feminino , Humanos , Ligadura , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Resultado do Tratamento
4.
Pediatr Int ; 59(7): 807-811, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28387991

RESUMO

BACKGROUND: Although complete excision is the standard treatment for pyriform sinus fistula (PSF), it has recently been suggested that chemocauterization via the internal orifice of the fistula could be an effective non-invasive treatment for the condition. The present report describes the details of our experience with and the efficacy of endoscopic chemocauterization for pediatric PSF. METHOD: Between January 2010 and June 2015, four patients were diagnosed with PSF and scheduled to undergo endoscopic chemocauterization. Under general anesthesia, trichloroacetic acid (TCA) solution was endoscopically injected through the opening of the fistula using a fine plastic tube. Esophagogram was obtained at 3 weeks after the procedure to search for recurrence. Complete closure of the fistula was confirmed on endoscopy at 2-3 months after chemocauterization. RESULTS: Two of the four patients were treated once, and the remaining patients required further chemocauterization procedures. No recurrence developed in any patient after it had been confirmed that the fistula's internal orifice had been obliterated. Some transient complications, such as sore throat, nausea or temporary vocal fold paresis, occurred. CONCLUSION: Chemocauterization with TCA seems to be a useful first-choice treatment for PSF.


Assuntos
Cáusticos/uso terapêutico , Cauterização/métodos , Endoscopia , Doenças Faríngeas/cirurgia , Seio Piriforme/cirurgia , Fístula do Sistema Respiratório/cirurgia , Ácido Tricloroacético/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Masculino
5.
Proc Natl Acad Sci U S A ; 114(9): E1688-E1697, 2017 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-28137855

RESUMO

The ovarian reserve represents the stock of quiescent primordial follicles in the ovary which is gradually depleted during a woman's reproductive lifespan, resulting in menopause. Müllerian inhibiting substance (MIS) (or anti-Müllerian hormone/AMH), which is produced by granulosa cells of growing follicles, has been proposed as a negative regulator of primordial follicle activation. Here we show that long-term parenteral administration of superphysiological doses of MIS, using either an adeno-associated virus serotype 9 (AAV9) gene therapy vector or recombinant protein, resulted in a complete arrest of folliculogenesis in mice. The ovaries of MIS-treated mice were smaller than those in controls and did not contain growing follicles but retained a normal ovarian reserve. When mice treated with AAV9/MIS were paired with male breeders, they exhibited complete and permanent contraception for their entire reproductive lifespan, disrupted vaginal cycling, and hypergonadotropic hypogonadism. However, when ovaries from AAV9-MIS-treated mice were transplanted orthotopically into normal recipient mice, or when treatment with the protein was discontinued, folliculogenesis resumed, suggesting reversibility. One of the important causes of primary ovarian insufficiency is chemotherapy-induced primordial follicle depletion, which has been proposed to be mediated in part by increased activation. To test the hypothesis that MIS could prevent chemotherapy-induced overactivation, mice were given carboplatin, doxorubicin, or cyclophosphamide and were cotreated with AAV9-MIS, recombinant MIS protein, or vehicle controls. We found significantly more primordial follicles in MIS-treated animals than in controls. Thus treatment with MIS may provide a method of contraception with the unique characteristic of blocking primordial follicle activation that could be exploited to prevent the primary ovarian insufficiency often associated with chemotherapy.


Assuntos
Hormônio Antimülleriano/farmacologia , Antineoplásicos/efeitos adversos , Anticoncepcionais/farmacologia , Folículo Ovariano/efeitos dos fármacos , Reserva Ovariana/efeitos dos fármacos , Animais , Anticoncepção/métodos , Dependovirus/metabolismo , Feminino , Células da Granulosa/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Insuficiência Ovariana Primária/prevenção & controle , Reprodução/efeitos dos fármacos
6.
Gen Thorac Cardiovasc Surg ; 63(10): 583-5, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24113995

RESUMO

Slide tracheoplasty is a standard treatment for long-segment congenital tracheal stenosis (LCTS). However, in severe cases of LCTS, aggressive divisions of inferior constrictor muscle from the thyroid cartilage and extensive circumferential dissection of the upper tracheal segment are often necessary to mobilize the upper tracheal segment enough to make an anastomosis, but they increase the risks of anastomotic dehiscence, recurrent nerve injury, and impaired deglutition. Alternatively, laryngeal release provides safe mobilization of the upper tracheal segment, minimizing dissection of the inferior constrictor muscle and preserving the lateral tissue pedicle without circumferential dissection. We successfully performed laryngeal release with slide tracheoplasty on six patients with severe LCTS, and report our findings.


Assuntos
Constrição Patológica/cirurgia , Laringe/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Traqueia/anormalidades , Traqueia/cirurgia , Constrição Patológica/diagnóstico , Feminino , Humanos , Lactente , Masculino
7.
Liver Transpl ; 19(11): 1202-13, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23894066

RESUMO

Graft fibrosis is a common finding during protocol biopsy examinations after pediatric liver transplantation. We evaluated the clinical utility of liver stiffness measurements by acoustic radiation force impulse (ARFI) imaging, a novel ultrasound-based elastography method, for assessing graft fibrosis after pediatric living donor liver transplantation (LDLT). We performed 73 liver stiffness measurements by ARFI imaging in 65 pediatric LDLT recipients through the upper midline of the abdomen (midline value) and the right intercostal space (intercostal value) around the time of protocol biopsy examinations. Fifty-nine of these liver stiffness measurements could be compared with histopathological findings. Graft fibrosis was assessed according to the degrees of portal and pericellular fibrosis. Significant fibrosis, which was defined as F2 or worse portal fibrosis and/or moderate or worse pericellular fibrosis, was observed in 14 examinations, which had significantly higher midline (P = 0.005) and intercostal values (P < 0.001) than the others. Liver stiffness measurements by ARFI imaging significantly increased with increases in the portal and pericellular fibrosis grades. For the diagnosis of significant fibrosis, the areas under the receiver operating characteristic curve (AUROCs) were 0.760 (P = 0.005) and 0.849 (P < 0.001) for the midline and intercostal values, respectively. The optimal cutoff values were 1.30 and 1.39 m/second for midline and intercostal values, respectively. Slight but significant elevations were noted in the results of biochemical liver tests: serum levels of γ-glutamyltransferase showed the highest AUROC (0.809, P = 0.001) with an optimal cutoff value of 20 IU/L. In conclusion, liver stiffness measurements by ARFI imaging had good accuracy for diagnosing graft fibrosis after pediatric LDLT. The pericellular pattern of fibrosis was frequently observed after pediatric LDLT, and moderate pericellular fibrosis was detectable by ARFI imaging.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Cirrose Hepática/diagnóstico , Transplante de Fígado/efeitos adversos , Doadores Vivos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Projetos Piloto , gama-Glutamiltransferase/sangue
8.
J Laryngol Otol ; 119(10): 828-30, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16259665

RESUMO

Haemangioma of the thyroid gland is extremely rare. We report a case of a cavernous haemangioma of the neck that was located both inside and outside the thyroid gland of a 21-year-old man. Ultrasonography of the neck revealed numerous calcified nodules. Computed tomography (CT) showed a large calcified soft tissue mass in the right lobe of the thyroid. Based on the imaging findings a papillary thyroid carcinoma was suspected, but examination of the surgical specimen revealed a huge cavernous haemangioma containing numerous phleboliths.


Assuntos
Hemangioma Cavernoso/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Adulto , Carcinoma Papilar/diagnóstico , Diagnóstico Diferencial , Hemangioma Cavernoso/patologia , Humanos , Masculino , Neoplasias da Glândula Tireoide/patologia
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