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[Factors considered to choose type of a hysterectomy for benign uterus lesions (excluding prolapsus and obstetrical indications)].

OBJECTIVES: We searched for the factors determining the type of hysterectomy (vaginal, laparoscopy or laparotomy) performed in women with supposedly benign uterine disease. MATERIAL AND METHOD: We conducted a retrospective study of 101 consecutive hysterectomies performed on voluminous uteruses, prolapsus and obstetrical indications excluded. The following factors likely to have influenced the decisions were examined: patient age, nulliparity, menopausal status, history of laparotomy, uterus weight, narrow vagina, nature of uterus lesions, associated unilateral or bilateral annexectomy, complications. RESULTS: The frequencies were: vaginal route 58.4% (average uterine weight 249.4 g, range 93-1149 g), laparoscopic preparation 37.6% (average uterine weight 348 g, range 92-818 g), and laparotomy 4% (average uterine weight 586.2 g, range 112-1216 g). Factors determining type of hysterectomy were uterine weight (and therefore volume) (p < 0.05), nulliparity (p < 0.04), narrow vagina probed by compulsory Schuchardt incision (p < 0.02), associated annexectomy (p < 0.01). No other factors were significantly determinant. The vaginal route appears to be highly preferred. CONCLUSION: Vaginal hysterectomy is clearly the most preferred and practiced. Laparoscopy may be helpful for vaginal hysterectomy and laparotomy is exceptional.

Age Factors↗

Distribution of viral antigen in uterus, placenta and foetus of cattle persistently infected with bovine virus diarrhoea virus.

The tissue distribution and cellular localisation of bovine virus diarrhoea virus (BVDV) was investigated in the uterus, placentomes, intercotyledonary foetal membranes and foetal organs of three persistently infected (PI) pregnant heifers. The uterus and ovaries of a non-pregnant PI heifer were also included in the study. Cryostat sections were examined using immunohistochemical techniques and monoclonal antibodies against BVDV. A double immunofluorescence technique was used to identify BVDV positive cells that also showed staining for either the leukocyte common antigen CD45 or the cytoskeletal filament vimentin. BVDV antigen was detected in all the organs examined, and was present in both epithelial and non-epithelial cells. In all organs many of the virus-positive cells also showed reactivity for vimentin. In the foetal liver and spleen a small, scattered population of virus-positive cells showed reactivity for CD45. A few cells showed reactivity both for BVDV antigen and for CD45 in the placentomes and intercotyledonary foetal membranes. In contrast to earlier reports, only scattered cells in the foetal part of the placentomes, the cotyledons, showed reactivity for BVDV antigen. However, in the chorion of the intercotyledonary foetal membranes, a larger proportion of the trophoblast cells showed reactivity for BVDV, especially the binuclear trophoblast cells. In the uterus, pregnancy appeared to favour virus replication, as the section from the pregnant heifers showed much stronger staining and a higher proportion of viral antigen-positive cells than sections from the non-pregnant PI heifer.

Animals↗

Diurnal changes in light intensity inside the pregnant uterus in sheep.

Penetration of light into the pregnant sheep uterus was studied in 9 ewes, gestational ages 40 to 142 days (term 147 days). Light sensors were placed inside the pregnant horn and over the flank skin overlying the position of the uterine horn. To perform the experiments, the ewes were placed in a study cage outdoors and light sensors were connected to a luxometer. Simultaneous measurements were obtained from the intrauterine and the external sensors in the shade at noon. The amount of light detected inside the uterus increased with gestational age from two lux at 40 days to 51.1 +/- 16.5 (n = 5) lux at 142 days (0.2 and 5.4% of the amount of light detected at the maternal flank). Measurements through the 24 h were done in four pregnant ewes at 142 days gestation under natural photoperiod (13.5 light:10.5 dark). In these experiments, the intensity of intrauterine light changed through the 24 h, reflecting the changes in the intensity of the sunlight. Maximal intrauterine light values were observed at noon, corresponding to 4.7% of incident light. Small but detectable values were observed at 0900 and 1800 h. Our data show that, at mid gestation, light reaches the pregnant uterus and that, at late gestation, changes in intrauterine lighting throughout the 24 h are present reflecting the changes in external daylight. Therefore the sheep fetus is exposed to light-dark transitions at dawn and dusk, and to a peak of light at midday.

Animals↗

Norgestomet- and oestradiol valerate-induced luteolysis is dependent upon the uterus.

Beef heifers were assigned to three groups: (1) untreated controls (n=4), (2) Syncro-Mate B(R) (SMB)-treated (n=5), and (3) hysterectomized and SMB-treated (n=4). SMB was administered 8 or 9 days after oestrus, approximately 30 days after hysterectomy. This study was conducted to determine if the uterus was necessary for SMB to induce luteolysis. SMB induced premature luteolysis as only 20% of the intact SMB-treated heifers had >/=0.75 ng/ml of progesterone 7 days after the time of SMB treatment, compared to all (100%) of the untreated heifers (p<0.05). By 9 days after the time of SMB treatment, 25% of the untreated heifers and none (0%) of the intact SMB-treated heifers had >/=0.75 ng/ml of progesterone; however, all (100%) of the hysterectomized SMB-treated heifers had >/=0.75 ng/ml of progesterone (p<0.05). Therefore, SMB-induced luteolysis required the involvement of the uterus. The luteolysin, prostaglandin F(2alpha), is probably the secretion from the uterus that mediates the SMB-induced luteolysis. SMB treatment, however, required 7-8 days to induce luteolysis.

Animals↗

Pharmacological effects of Agapanthus africanus on the isolated rat uterus.

The Agapanthus africanus plant is used by South African traditional healers as a phytomedicine in herbal remedies to treat pregnancy-related ailments and to augment labour. It has already been shown that an aqueous extract of A. africanus causes smooth muscle contractions in the isolated uterus and ileum preparations. In the present study, the effects of an aqueous extract of A. africanus leaves was examined on receptor systems involved in contraction of the uterine smooth muscle in order to determine the mechanism of its pharmacological effect relevant to its ethnic use to augment labour. The extract was tested on the isolated rat uterus preparation. The aqueous extract of A. africanus leaves was found to exhibit agonist activity on uterine muscarinic receptors and to promote the synthesis of prostaglandins in the oestrogenized rat uterus. Some pharmacological justification for the ethnic use of A. africanus as a herbal oxytocic in prolonged labour has been provided.

Acetylcholine↗

Novel Calbindin-D(9k) protein as a useful biomarker for environmental estrogenic compounds in the uterus of immature rats.

The compounds that bind the estrogen receptors (ER) and induce or modulate an ER-mediated response can be defined as estrogenic endocrine disruptors (EDs). We demonstrated that environmental estrogens induced the uterine CaBP-9k mRNA in rats using Northern blot assay suggesting that CaBP-9k gene could be a biomarker for the estrogenicity of chemicals in the previous studies. In the present studies, we further collaborated this idea by investigating the regulation and localization of CaBP-9k protein in response to estrogenic compounds. Immature rats were injected with estrogenic chemicals, 4-tert-octylphenol (OP), nonylphenol (NP) and bisphenol A (BPA) or 17beta-estradiol (E2). After treatment with these estrogenic compounds, the effects on the accumulation of CaBP-9k protein and uterine localization were examined by Western blot analysis and immunohistochemical staining (IHC), respectively. A dose- and time-dependent increase in CaBP-9k protein was observed in the uterus of immature rats when treated with OP and NP. In addition, treatment with BPA resulted in a significant increase in CaBP-9k protein at dose of 500mg/kg BW/day. Taken together, CaBP-9k protein is strongly up-regulated by estrogenic compounds (OP, NP and BPA) and E2 itself in the uterus of immature rats. These results indicate that CaBP-9k protein can be a useful biomarker for detection of the estrogenicity of putative estrogenic compounds. Thus, regarding to risk assessment, we propose that CaBP-9k protein assay in the immature rat uterus can be a very sensitive and powerful tool to identify compounds with estrogenic activity when used in combination with classical assays.

Animals↗

Can the irradiated uterus sustain a pregnancy? A literature review.

A significant number of adult pre- menopausal women are offered pelvic radical radiotherapy as part of the management of their malignancy. Advances in human reproductive research are making pregnancy a possibility for these women, but ovarian function, however, is not the only requirement for establishing and maintaining a pregnancy that will result in the delivery of a normal infant. The processes of implantation, fetal and placental development and labour require normal cervical structure and function. Radiation induces acute and late changes in the uterus that have a permanent impact. This article aims to summarise the published data on this complex subject. To date, the majority of reports of successful pregnancies refer to women who had hemi-pelvis or abdominal irradiation suggesting that partial volume irradiation of the uterus may not preclude pregnancy. However, with the current available information, women receiving a radical dose of radiotherapy to the whole uterus are very unlikely to have a successful pregnancy even if ovarian function is maintained. Systematic studies and, in particular, studies looking at modern radiotherapy techniques are required, as well as a register of pregnancies and outcomes to be able to provide answers for this group of patients.

Adult↗

Role of nitric oxide on oxytocin-evoked contractions and prostaglandin synthesis in isolated pregnant rat uterus.

Uterine contractions elicited by oxytocin (OT), possibly linked with uterus prostaglandin (PG) release, are involved in the final pathway of labor. It is known that nitric oxide (NO) may contribute to the maintenance of uterine contractile quiescence during gestation. Therefore in this study the effect of the inhibition of NO synthase (NOS), with N-monomethyl L-arginine (L-NMMA), on the ability of OT to stimulate uterine contractions and PG synthesis was investigated in isolated rat uterus at days 13 and 21 of pregnancy. L-NMMA did not modify the frequency and the force of contractions elicited by OT at day 13. On day 21 the frequency of contractions evoked by OT were better sustained in the presence of L-NMMA. PGs were not affected by OT on day 13. OT stimulated PGF2alpha on day 21 when NOS had been inhibited with L-NMMA, but not in the absence of L-NMMA. NOS activity was stimulated by OT at day 21 of gestation. In summary these findings indicate that near term NO can regulate OT PGF2alpha induced contractions and PG synthesis in isolated pregnant rat uterus.

Animals↗

DT56a (Tofupill/Femarelle) selectively stimulates creatine kinase specific activity in skeletal tissues of rats but not in the uterus.

The novel natural product DT56a (Tofupill/Femarelle), derived from soybean, has been shown to relieve menopausal vasomotor symptoms and to increase bone mineral density with no effect on sex steroid hormone levels or endometrial thickness. In the present study, we compared the effects of DT56a and estradiol-17beta (E2) on bone and cartilage (Ep) of immature or ovariectomized female rats, by measuring the changes in the specific activity of the BB isozyme of creatine kinase (CK). Single short-term injection of high doses of DT56a induced estrogenic activity in bones and uterus similar to that of E2. When administered in multiple oral doses, DT56a stimulated skeletal tissues similarly to E2, but whereas E2 increased CK specific activity in the uterus, DT56a did not. The selective estrogen receptor modulator (SERM) raloxifene (Ral) blocked the stimulation of CK by either DT56a or by E2 in all tissues tested. Our findings suggest that DT56a acts as a selective estrogen receptor modulator stimulating skeletal tissues without affecting the uterus. The effect of DT56a on other systems, such as the vascular and the central nervous system, are currently under investigation.

Animals↗

Estrogen-induced genes in the uterus of ovariectomized rats and their regulation by droloxifene and tamoxifen.

The identification and characterization of estrogen regulated genes in reproductive tissues is an important step in understanding estrogen's mechanism of action in sexual development and neoplasia. It is also important, given the clinical interest, to evaluate the molecular effects of estrogen agonists/antagonists such as tamoxifen and droloxifene in reproductive tissues. In this report, our goal was to identify estrogen regulated genes in the uterus and to compare the regulation by estrogen and tamoxifen with that of droloxifene. A subtractive cDNA library strategy was developed to identify estrogen-regulated genes in the uteri of ovariectomized rats 4 h after treatment with 17-alpha-ethynyl estradiol (30 microg/kg). The mRNAs encoding 8 genes were confirmed by Northern blot analysis to be induced at early times following estrogen administration. Calcium binding protein 9 kDa and complement protein 3 are well characterized estrogen regulated genes that were identified in the library and served as markers for estrogen action. In addition, mRNAs encoding the interleukin 4 receptor, heat-shock protein 70 kDa, metallothionein, tumor necrosis factor regulated gene 6, inositol-1-monophosphate synthase, and cyr-61 were induced in the uterus by estrogen. The identified mRNAs were then examined for regulation by droloxifene (1 and 10 mg/kg, p.o.) and tamoxifen (10 mg/kg, p.o.). Both droloxifene and tamoxifen induced mRNA levels for all of these genes. However, clear quantitative and temporal differences were observed when comparing estrogen versus droloxifene versus tamoxifen. For example, estrogen induced IL4 receptor mRNA to a greater degree than did tamoxifen or droloxifene. Conversely, tamoxifen resulted in a much greater induction of cyr61 than did either estrogen or droloxifene. Droloxifene at 1 mg/kg, an efficacious dose for prevention of bone loss in this model, did not or only slightly induced the mRNA for all of the genes examined with the exception of cyr61. In conclusion, the modified subtractive library method used in this study proved to be efficient in the identification of estrogen-regulated genes in the uterus. The identities of the regulated genes were consistent with the concept that estrogen functions to prime uterine tissue for increased responsivity to extracellular signals such as growth factors and cytokines. Elucidating the physiological role of these newly identified estrogen responsive genes and the mechanisms responsible for the different responses to droloxifene versus estrogen and tamoxifen may be important in enhancing our understanding of tissue selective estrogen agonists/antagonists.

Animals↗

Regulation of thioredoxin mRNA in the rat uterus by gonadal steroids.

Estradiol has been shown to increase the level of thioredoxin mRNA in the uterus of the ovariectomized (ovx) rat. In this study the influence of progesterone, androgens, the anti-estrogen ICI 182780 and the anti-androgen Flutamid on thioredoxin expression, has been studied in the rat uterus. Thioredoxin mRNA concentrations were determined by solution hybridization. Ovx rats treated with progesterone alone showed no effect on thioredoxin expression. Combined treatment of ICI 182780 and estradiol attenuated the estradiol-induced increase in thioredoxin mRNA. When ovx rats were treated with a testosterone depot, the amount of thioredoxin mRNA was increased five-fold after 48 h and remained at that level during the rest of the 168 h monitored. A similar increase in thioredoxin mRNA could be seen after 5alpha-dihydrotestosterone treatment, indicating a true androgenic effect. In addition, the anti-androgen Flutamid attenuated the thioredoxin mRNA increase seen after 5alpha-dihydrotestosterone treatment alone. It is concluded that thioredoxin mRNA is regulated by growth promoting gonadal steroids in the rat uterus. The attenuation of the estrogen and androgen-induced increases of the thioredoxin mRNA with ICI 182780 and Flutamid, indicate that the effect is mediated via the estrogen receptor and androgen receptor respectively. None of these hormones affected the hepatic thioredoxin mRNA level in the same animals.

Androgens↗

Interaction between oxytocin and 'sidaverin' on the gravid and non-gravid rat uterus.

Sidaverin, a crystalline compound extracted from a polar fraction of Sida veronicaefolia (Lam), elicited oxytocin-like contractions in the non-gravid rat isolated uterus preparation with a concentration-response relationship. Equipotent concentrations of oxytocin and sidaverin, using matched responses, were approximately 0.16 U and 0.4 micrograms ml-1, respectively. Sidaverin-induced contractile response was atropine reversible. The concentration-response curves for sidaverin and oxytocin were parallel, and both responses were inhibited by the specific oxytocin antagonist, Atosiban, indicating possible involvement of oxytocin receptors in the action of sidaverin. There were potentiation of action of one drug to that of the other, irrespective of the order of administration and even after washing off the first before introducing the second drug. In the gravid uterus, sidaverin produced contractions in preparations from day 1 to day 6 or 7, caused relaxation in days 7-11, and elicited contractions in day 11 through term, the sensitivity of the preparations increasing exponentially toward term with strong sustained contractions. With the exception of days 7-11, when sidaverin antagonized oxytocin action, it potentiated action of oxytocin on the gravid uterus.

Acetylcholine↗

Metroplasty for the complete septate uterus: does cervical sparing matter?

STUDY OBJECTIVES: To verify if section of the cervical septum facilitates hysteroscopic metroplasty of a complete septate uterus, and to determine if this technique is associated with intraoperative bleeding or postoperative obstetric complications. DESIGN: Prospective, observational study. SETTING: Academic department and tertiary care referral center for malformations of the female genital tract. PATIENTS: Ten women with complete septate uterus. INTERVENTIONS: The cervical portion of the septum was incised with Metzenbaum scissors and the corporeal portion with microscissors under hysteroscopic guidance. MEASUREMENTS AND MAIN RESULTS: Mean +/- SD operating time for the entire procedure was 24 +/- 7 minutes, with a mean distention fluid deficit of 480 +/- 190 ml. No significant bleeding was encountered during cervical septum incision. At follow-up hysteroscopy, the cervices were competent, and no women experienced second-trimester abortion or premature delivery. CONCLUSIONS: Section of the cervical septum with scissors is simple, rapid, and safe, facilitates corporeal hysteroscopic metroplasty, and may be considered a valid procedure to correct a completely septate uterus.

Cervix Uteri↗

[Non-Hodgkin's lymphoma of the uterus: apropos of 4 cases and review of the literature].

The primary non hodgkin's lymphoma of the uterus is rare. This rarity explains of one part certain difficulties of the histological diagnosis and on the other hand the absence of a therapeutic strategy clearly established. We report 4 cases of primary non-hodgkin lymphoma of the uterus. Two patients had a cervical location, the two other had corpus location. The average age of our patients is of 59 years (extremes: 54-68). Histological diagnosis was confirmed by biopsy for the cervical location. For the corpus location, it is study of the uterus after hysterectomy which retained the diagnosis of lymphoma. The type of the lymphoma was low grade in two cases and high grade in the two other cases. The disease was limited to the pelvis for all our patients (stage IE according to Ann-Arbor's classification). The treatment consisted of an association of chemotherapy and radiotherapy in both cases of lymphoma of the cervix and in a radical hysterectomy followed by chemotherapy for the two cases of lymphoma of the corpus. Our patients are regularly followed, with an average follow-up of 56 months. Two patients are in disease free, the third patient presented a dissemination of the disease and the fourth patient presented a squamous cell carcinoma of the lung.

Aged↗

[Septate uterus and reproduction disorders: current results of hysteroscopic septoplasty].

Uterus septus is the most frequent congenital uterine anomalies caused by insufficient resorption of the müllerian ducts. Retrospective statistical analysis shows that the uterine septa have the worst reproductive outcome with a high incidence of early abortions. It is well recognized that it increased the incidence of recurrent (> or = 3) miscarriages (79% among 1,601 pregnancies), reproductive failure and obstetric complications. A septate uterus does not seem to be an infertility factor. On the other hand, the incidence of unexplained infertility was significantly higher (40%) in the patients with secondary infertility; thus, a contribution from the uterine septum in delayed conception of these patients cannot be excluded. Hysteroscopic surgery has replaced conventional abdominal route. Hysteroscopic metroplasty improves obstetrical prognosis in women with septate uterus, and it's advantages are easiness, low morbidity rate, without the hysterotomy's consequences like adnexial adhesions. Metroplasty is indicated in women with a history of miscarriages (2 or more), which decreased to 15%, in patients with an unexplained infertility, and in women in whom assisted reproductive treatment is being contemplated. Combined with laparoscopy, the hysteroscopic metroplasty is the gold standard for assessing uterine septa, especially in these infertile women. Laparoscopy also is required to complete the diagnostic work up of infertility, and provides an opportunity to treat any coexisting pelvic pathology.

Abortion, Spontaneous↗

Rat GST 8-8 is expressed predominantly in myeloid origin cells infiltrating the gravid uterus.

Previous studies from our laboratory have shown a relatively high expression of rGST8-8 in uterine tissues. This GST isozyme displays relatively high glutathione-peroxidase activity towards lipid-hydroperoxides and towards toxic 4-hydroxyalkenals generated from lipid peroxidation. Since the uterus is a unique organ, subject to oxidative stress due to infiltration by immune effector cells during gestation and because this infiltration is readily identifiable histologically, the studies reported herein were performed to localize the cell specific expression of rGST8-8 to determine whether immune effector cells infiltrating the pregnant rat uterus specifically expressed rGST8-8. A 75 bp end-radiolabeled cRNA probe was prepared from the full length mGSTA4-4 cDNA from the region which is highly homologous with rGST8-8. This cRNA probe was used for in situ hybridization studies to localize rGST8-8 in specific cell types of gravid rat uterus. Results of these studies indicate that this GST isozyme is selectively expressed in myeloid origin cells such as monocytes/macrophages, and neutrophils infiltrating the uterine endometrium and in vascular walls. Selective expression of rGST8-8 in the myeloid origin cells, which are known to generate higher levels of reactive oxygen species, suggests that this GST isozyme plays an important role in the protection mechanisms against lipid peroxidation.

Animals↗

A case of successful twin pregnancy placed in separate horns of bicornuate, unicollis uterus.

We described a case of pregnancy, delivery and peurperium of 28 years old multipara with twins pregnancy in bicornuate, unicollis uterus. Each fetus was placed in separate horn of uterus. Biological mature pregnancy was delivered by cesarean section. During the peurperium the involution disturbances of one of the uterus horns were observed. The case was discussed in context of other similar anomalies.

Adult↗

Estrogen-induced changes in high-energy phosphate metabolism in rat uterus: 31P NMR studies.

Changes in the concentrations of high-energy phosphate metabolites were measured by 31P NMR spectroscopy of surviving rat uteri from 0-48 h following estrogen administration. Concentrations (millimoles per kilogram wet weight) of these metabolites in the untreated immature uterus, measured at 4 degrees C, were found to be the following: creatine phosphate (CP), 2.1 +/- 0.2; nucleoside triphosphates, mainly adenosine 5'-triphosphate (ATP), 4.6 +/- 0.4; phospho monoesters, primarily sugar phosphates (SP), 5.4 +/- 0.7; and inorganic phosphate (Pi), 0.8 +/- 0.4. Adenosine 5'-diphosphate (ADP) concentration was estimated to be approximately 40 mumol/kg wet weight from the assumed equilibrium of the creatine kinase reaction. The concentration of CP, and to lesser extent ATP and SP, declined within the first 1.5-3 h after injection of 17 beta-estradiol, returned to control values between 6 and 12 h, and then increased, reaching maximal concentrations at 24 h. From the fractions of the total soluble ATP in free and Mg2+-bound forms, [free Mg2+] in the untreated uterus was estimated to be 0.2-0.4 mmol/kg wet weight. An increase in [free Mg2+] in the uterus was detected 1.5 h after estrogen injection. A subsequent parallel increase in the ratio of ATP to CP concentrations suggests that estrogen can also affect the apparent creatine kinase equilibrium by modulating [free Mg2+].

Adenosine Diphosphate↗