Assuntos
Amenorreia/diagnóstico , Cicatriz/complicações , Ginatresia/diagnóstico , Complicações na Gravidez/cirurgia , Gravidez Ectópica/terapia , Adulto , Amenorreia/etiologia , Cesárea/efeitos adversos , Diagnóstico Diferencial , Embolização Terapêutica/efeitos adversos , Feminino , Ginatresia/etiologia , Humanos , Histeroscopia , Gravidez , Curetagem a Vácuo/efeitos adversosRESUMO
Uterine fibroids are considered to be the most frequently occurring tumours in females. The majority of fibroids do not require any treatment. When symptomatic, the major ailments include abnormal uterine bleeding, painful menstruation, pelvic pressure or pain, urinary problems, constipation, infertility, and recurrent pregnancy loss. Surgery remains a mainstay of symptomatic uterine fibroids therapy; however, minimally-invasive techniques and pharmacological management have become more available. The levonorgestrel intrauterine system (LNG-IUS) is a T-shaped device with a vertical stem containing a reservoir of levonorgestrel and is widely known for its contraception effect. Moreover, the non-contraceptive benefits of the LNG-IUS have been previously confirmed by numerous studies. LNG-IUS causes reduction of the duration and the amount of menstrual bleeding, with minimal side effects due to release of hormones at the targeted organ. Currently, results from systematic reviews show that LNG-IUS may be an effective and safe treatment for symptomatic uterine fibroids in premenopausal women. However, further studies are required to consolidate the usage of LNG-IUS in the treatment of symptomatic uterine fibroids.
RESUMO
Uterine fibroids are considered to be the most frequent female benign tumours. Fibroids affect mainly women of reproductive age. The most frequently reported signs and symptoms of fibroids include disturbances of the menstrual cycle such as heavy bleeding and painful menstruation, pelvic masses associated with pelvic pain, urinary problems or constipation, as well as infertility and recurrent pregnancy loss. The mainstay of fibroid treatment is still surgery. However, many patients seek alternative treatment options for fibroids, to preserve their uterus and fertility. One of the most important alternative treatment options for fibroids is uterine artery embolisation (UAE). However, there are some concerns that UAE may negatively influence ovarian function and even result in premature menopause. Moreover, the use of UAE in patients with future reproductive plans is still controversial, due to the possible pregnancy complications. The purpose of this review is to summarise the current knowledge regarding the possible influence of UAE on fertility, pregnancy outcome, and ovarian reserve.
RESUMO
INTRODUCTION AND OBJECTIVE: Uterine artery embolization (UAE) is a minimally invasive treatment option for symptomatic fibroids. Long-term follow-up studies have shown that at five-year follow-up after UAE, up to 30% of patients required a hysterectomy. Therefore, it seems of utmost importance to identify patients, who are unlikely to benefit from UAE. It has been postulated that the percentage volume reduction of fibroids may predict long-term UAE outcome. The results of available studies are equivocal, therefore it seemed of interest to investigate the correlation between the preinterventional intramural fibroid volume and imaging outcome of UAE in premenopausal patients. MATERIAL AND METHODS: Uterine artery embolization was performed in 65 premenopausal patients with symptomatic, intramural fibroids. Dominant fibroid volume was assessed using an integrated VOCAL (Virtual Organ Computer-aided AnaLysis) imaging program at baseline and 3 months after UAE. The percentage reduction of fibroid volume was calculated. The association between preinterventional fibroid volumes and percentage volume reductions was determined with the Spearman rank correlation test. RESULTS: Before UAE, the median dominant fibroid volume was 101 cm(3) (range 23.6-610). At three-month follow-up the median dominant leiomyoma volume decreased to 50.4 cm(3) (range 6.9-193.9). Median percentage reduction of fibroid volume three months after UAE was calculated at 50.1% (range 2.7-93.5). The Spearman correlation test between the preinterventional dominant fibroid volume and percentage volume reduction showed a statistically significant, positive correlation (R = 0.33; p = 0.006). CONCLUSIONS: The percentage volume reduction of intramural leiomyomas after UAE seems to be more pronounced in the case of larger tumors.
RESUMO
The aim of the study was to present clinical issues concerning uterine artery embolization (UAE) in women with uterine fibromas. In order to ensure high clinical efficiency of UAE and prevent subsequent complications, it is necessary to carefully select patients eligible for the procedure. Patients with intramural fibromas, who do not plan to conceive, are the best candidates for the procedure. Fibroma necrosis, with following infection, and premature ovarian failure remain to be the most common complications after UAE. UAE may cause amenorrhea and increase FSH levels, what is typical for menopause. Thus, it may be responsible for problems with conception as well as optimal development of a pregnancy. It may also cause premature, iatrogenic menopause. This complication significantly more frequently occurs in women over the age of 45 as compared to younger patients. UAE is considered as an alternative therapeutic procedure, available to women who do not desire the surgery or wish to preserve the uterus. Patients subject to this procedure should be informed about the possible side effects.
Assuntos
Amenorreia/etiologia , Infertilidade/etiologia , Leiomioma/etiologia , Insuficiência Ovariana Primária/etiologia , Embolização da Artéria Uterina/efeitos adversos , Adulto , Feminino , Humanos , Menopausa Precoce , Pessoa de Meia-Idade , Necrose/etiologia , Gravidez , Útero/patologiaRESUMO
Herein, we describe the discovery of potent and highly selective inhibitors of both CDK4 and CDK6 via structure-guided optimization of a fragment-based screening hit. CDK6 X-ray crystallography and pharmacokinetic data steered efforts in identifying compound 6, which showed >1000-fold selectivity for CDK4 over CDKs 1 and 2 in an enzymatic assay. Furthermore, 6 demonstrated in vivo inhibition of pRb-phosphorylation and oral efficacy in a Jeko-1 mouse xenograft model.
RESUMO
A search for noncarbohydrate sLe(x) mimics led to the development of quinic acid derivatives as selectin inhibitors. At Wyeth we solved the first cocrystal structure of a small molecule, quinic acid, with E-selectin. In the cocomplex two hydroxyls of quinic acid mimic the calcium-bound fucose of the tetrasaccharide sLe(x). The X-ray structure, together with structure based computational methods, was used to design quinic acid based libraries that were synthesized and evaluated for their ability to block the interaction of sLex with P-selectin. A large number of analogues were prepared using solution-phase parallel synthesis. Selected compounds showed decrease in leukocyte rolling in the IVM mouse model. Compound 2 inhibited neutrophil influx in the murine TIP model and demonstrated good plasma exposure.