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Uterus didelphys associated with obstructed hemivagina and ipsilateral renal agenesis: MR findings in seven cases.

BACKGROUND: Although a specific syndrome of the uterus didelphys, obstructive hemivagina, and ipsilateral renal agenesis had been reported in gynecologic literatures, it is not familiar to radiologists. We introduce this syndrome with radiological, especially MR findings. METHODS: Imaging findings and medical records of seven patients with this syndrome were retrospectively reviewed. RESULTS: MR clearly demonstrated uterus didelphys with obstructed hemivagina in six of the seven patients. A remaining one showed uterus didelphys with left-sided hematometra and hematosalpinx who had undergone vaginal septum incision prior to the MR. We could also recognize ipsilateral renal agenesis in all five patients, in whom renal areas were examined on MR. After vaginal septum resection, symptoms disappeared in six patients. We could observe the disappearance of the obstructive complications with MR in three patients. CONCLUSIONS: MR can do much for the early diagnosis and the prevention against further complications of this condition because it can demonstrate the müllerian duct anomaly complicated with obstructed hemivagina in detail and even ipsilateral renal agenesis.

Adolescent↗

Reproductive outcome of septate uterus after hysteroscopic metroplasty.

We evaluated the reproductive outcome after hysteroscopic metroplasty in the patients with septate uterus. The reproductive performance of 361 patients with septate uterus during the follow-up period of 18 months after the surgery was analyzed retrospectively for a period of 10 years. A total of 180 (49.8%) pregnancies were achieved after metroplasty during the follow-up period of 18 months. Of the 180 pregnancies 117 (57.2%) reached to term and 34 (18.8%) ended in preterm delivery and the remaining 29 (16%) resulted in abortion. Of the preterm babies 18 (52.9%) were able to live. We obtained 135 (75%) live babies totally. Hysteroscopic metroplasty improves the reproductive performance of septate uterus significantly especially in the cases with recurrent pregnancy loss and should be considered highly as a corrective approach for such patients.

Abortion, Spontaneous↗

Calretinin-immunoreactive nerves in the uterus, pelvic autonomic ganglia, lumbosacral dorsal root ganglia and lumbosacral spinal cord.

Nerves containing the calcium-binding protein calretinin have been reported in several organs but not in female reproductive organs and associated ganglia. This study was undertaken to determine if nerves associated with the uterus contain calretinin and the source(s) of calretinin-synthesizing nerves in the rat (are they sensory, efferent, or both?). Calretinin-immunoreactive nerves were present in the uterine horns and cervix where they were associated with arteries, uterine smooth muscle, glands, and the epithelium. Calretinin-immunoreactive terminals were apposed to neurons in the paracervical ganglia; in addition, some postganglionic neurons in this ganglion were calretinin positive. Calretinin perikarya were present in the lumbosacral dorsal root ganglia, no-dose ganglia, and lumbosacral spinal cord. Retrograde axonal tracing, utilizing Fluorogold injected into the uterus or paracervical parasympathetic ganglia, revealed calretinin-positive/Fluorogold-labeled neurons in the dorsal root and nodose ganglia. Also, capsaicin treatment substantially reduced the calretinin-positive fibers in the uterus and pelvic ganglia, thus indicating the sensory nature of these fibers. The presence of calretinin immunoreactivity identifies a subset of nerves that are involved in innervation of the pelvic viscera and have origins from lumbosacral dorsal root ganglia and vagal nodose ganglia. Though the exact function of calretinin in these nerves is not currently known, calretinin is likely to play a role in calcium regulation and their function.

Animals↗

Electrical and mechanical activity of rat uterus in vivo during the estrous cycle.

Electromyograms were obtained from three different locations on the uterus of conscious, unrestrained rats during the 4 day estrous cycle. Intrauterine pressure changes were monitored simultaneously by means of indwelling intraluminal balloons (vol. 0.02 to 0.05 ml.). Electrical activity consisted of bursts of action potentials that were usually initiated at either end of the uterus. Propagated burst activity gave rise to cyclic intrauterine pressure changes, whereas bursts appearing at one electrode only did not elicit any measurable contractions. The rate of intrauterine pressure development depended on the propagation velocity, whereas the tension achieved was related to the duration of burst activity. All three parameters of electrical activity studied, namely, the duration and frequency of spike bursts, as well as their rate of propagation, varied significantly during the cycle. Regional differences were also subject to cyclic variations; thus, in proestrus the bursts originated predominantly at the cervical end, whereas in diestrus they were usually initiated at the ovarian end. Oxytocin stimulated the frequency and duration of bursts along the whole uterus and elicited corresponding changes in intrauterine pressure. Response to oxytocin was dose dependent and modified by cycle stage. Norepinephrine caused a transient prolongation of burst activity that was not dose dependent; epinephrine had a marked dose-dependent inhibitory action. The response to catecholamines did not vary significantly during the cycle. The variations in electrical and mechanical activity were characteristic for each stage of the ovarian cycle and could be correlated with the well-known hormonal changes. High circulating estrogen levels in proestrus are associated with infrequent but rapidly propagated spike bursts, whereas low levels in estrus are associated with frequent and sometimes nonpropaged bursts. The rise in plasma estrogen in diestrus coincides with a decrease in the frequency of burst activity, and the elevated progesterone levels are probably causally related to the significant drop in propagation velocity and the increase in duration of bursts observed in diestrus. These findings are consistent with the concept that estrogen withdrawal activates the estrogen-primed, quiescent myometrium, and that progesterone has an effect similar to that of estrogen withdrawal--at least in the rat.

Action Potentials↗

Distribution of adrenergic receptors does not explain regional differences in blood flow in the pregnant rabbit uterus.

The increase in uterine blood flow during pregnancy is maximal at the placental implantation site, but the mechanisms of this increase are poorly understood. Adrenergic receptor activation may influence blood flow both directly and indirectly. We therefore asked whether distribution of myometrial adrenergic receptors within the rabbit uterus could explain the increased blood flow to smooth muscle under the placenta. alpha-Adrenergic and beta-adrenergic receptor concentrations and affinities were measured in myometrium from under the placenta and compared to myometrium between placentas and distant from the placentas. There were no differences in receptor concentrations or affinities in different parts of the uterus. We therefore conclude that the distribution of adrenergic receptors in the pregnant rabbit uterus cannot explain the preferential blood flow to myometrium at the placental implantation site.

Animals↗

Long-term effects of hormone replacement therapy on the uterus and on uterine circulation.

OBJECTIVE: Our purpose was to study the effects of postmenopausal hormone replacement therapy on the uterus and uterine circulation. STUDY DESIGN: The study population consisted of 432 women, 58 to 59 years of age. Color Doppler ultrasonography with a transvaginal probe was used to measure the size of the uterus and the uterine artery pulsatility index. RESULTS: The mean endometrial thickness in group 1 (controls without hormone replacement therapy) was significantly thinner compared with group 2 hormone replacement therapy and with group 3 after discontinuance of hormone replacement therapy. The mean uterine artery pulsatility index was lower both in group 2 and 3 compared with group 1. When hormone replacement therapy was initiated 2 to 10 years after menopause, the endometrial thickness did not differ from that among those who had started hormone replacement therapy earlier, but the pulsatility index was significantly higher. There was positive correlation between the size of the uterus and the pulsatility index in group 1, but the correlation was negative in group 2. In general, the duration of hormone replacement therapy had no effect on the pulsatility index. Estrogen users had a significantly thicker endometrium compared with estrogen-progestogen users. The pulsatility index was highest in the estrogen users with progestogen added every month. CONCLUSION: The duration, onset of treatment in relation to menopause, discontinuance of hormone replacement therapy, and mode of treatment modify both the normal postmenopausal endometrial thickness and the uterine vascular resistance.

Arteries↗

Estrogenic effects of the antiprogestin onapristone (ZK98.299) in the rodent uterus.

OBJECTIVE: Our purpose was to assess the estrogenic action of onapristone (ZK299). STUDY DESIGN: Three rodent models of estrogen action in the uterus were used. Deoxyribonucleic acid synthesis in the uterine epithelium of neonatal mice was determined by thymidine autoradiography. In adult ovariectomized mice uterine wet weight and progesterone receptor and estrogen receptor concentrations were determined. In immature rats uterine deoxyribonucleic acid synthetic activity was determined by thymidine autoradiography, epithelial hypertrophy and stromal edema were assessed histomorphometrically, and complement C3 protein synthesis was assessed by metabolic labeling in vitro. The effects of ZK299 were challenged with the antiestrogens ICI164,384 and tamoxifen. The ability of ZK299 to displace tritiated estradiol from the estrogen receptor was assessed in cytosolic preparations from mouse uterus. RESULTS: In the neonatal mouse ZK299 stimulated epithelial deoxyribonucleic acid synthesis; two other antiprogestins, RU486 and ZK98.734, had no effect. Three daily injections of ZK299 at 10 micrograms/gm body weight to 6-week-old ovariectomized mice increased uterine progesterone receptor 42%; this effect was blocked by ICI164,384. In another experiment three daily doses of ZK299 (20 micrograms/gm) to 10-week-old ovariectomized mice increased progesterone receptor concentration by 63% and uterine wet weight by 42%. In 21-day-old rats a single injection of ZK299 increased uterine epithelial deoxyribonucleic acid synthesis; this effect was blocked by tamoxifen. Both ZK299 and tamoxifen increased epithelial cell height and thymidine labeling in the stroma. ZK98.734 had no effect on epithelium or stroma. ZK299 also stimulated synthesis of complement C3 by uteri of immature rats. In competitive binding assays ZK299 exhibited weak relative binding affinity (0.05%) for mouse uterine estrogen receptor. CONCLUSIONS: ZK299 can act as a weak estrogen in the rodent uterus, most likely through a direct, low-affinity interaction with the estrogen receptor. Because estrogens may increase the risk for endometrial, breast, and liver cancer, caution is warranted in long-term administration of this drug to women.

Animals↗

Biosynthesis of prostaglandin F2alpha from arachidonic acid and prostaglandin endoperoxides in the uterus.

Formation of prostaglandin F2Alpha in the cow and guinea pig uterus microsomes was studied using 14C-labeled arachidonic acid and prostaglandin H2. The total conversion of arachidonic acid was of a low order and underwent fluctuations during the estrous cycle of the guinea pig, being highest towards the end of the cycle. Injections of beta-estradiol-3-benzoate also resulted in higher activity of the uterine prostaglandin synthetase. The uterine prostaglandin synthesizing system appeared to differ in several respects from that present in seminal vesicles, with regard to the proportions of the products formed and the effects of various agents, e.g. reduced glutathione. An inhibiting factor which supressed the fatty acid cyclo-oxygenase was found to be present in uterine preparations. Prostaglandin endoperoxide (prostaglandin H2) was very efficiently reduced to prostaglandin F2alpha by cow and guinea-pig uterus microsomes. Prostaglandin G2 also gave rise to prostaglandin F2alpha. Prostaglandin E2, on the other hand, was not reduced. Both the inhibiting factor and the endoperoxide reducing activity are likely to be parts of a highly specialized mechanism that modulates prostaglandin F2alpha formation in the uterus.

Animals↗

A novel 17 kD heparin-binding growth factor (HBGF-8) in bovine uterus: purification and N-terminal amino acid sequence.

We have purified to near homogeneity a novel 17 kD growth factor from bovine uterus which we designated heparin-binding growth factor-8 (HBGF-8). The growth factor binds tightly to cation exchange resins and to Heparin-Sepharose and is stable to acetone precipitation and labile in acid. Based upon total activity in acetone extracts of bovine uterus stimulating 3H-thymidine incorporation into DNA of serum-starved NIH 313 cells, a 6940 fold purification was achieved with an overall yield of HBGF-8 activity of 0.4%, using extraction of acetone powders and chromatographic separations at neutral pH. Approximately 18 micrograms protein was obtained from 1.2 kg wet weight of tissue. HBGF-8 was clearly separated from 17.5 kD bovine uterus basic fibroblast growth factor (bFGF) by purification and its N-terminal amino acid sequence analyzed. A polypeptide with a unique 25 N-terminal amino acid sequence was found. HBGF-8 was as active as acidic fibroblast growth factor (aFGF) and slightly less active than bFGF in the mouse NIH 3T3 fibroblast mitogenic assay system with an intrinsic specific activity of 5000 dpm/ng under standard assay conditions.

Amino Acid Sequence↗

Autoradiographic determination of catechol estrogen binding sites in brain, pituitary and uterus.

The anatomical pattern of nuclear binding of 2-OH[6,9-3H]estradiol ([3H]2-OHE2) in brain, pituitary and uterus have been studied autoradiographically. Autoradiograms of forebrain, pituitary and uterus show nuclear concentrations of radioactivity in certain cells. This nuclear concentration is abolished when unlabelled 2-OHE2 or E2 was injected prior to the injection of [3H]2-OHE2. In the brain nuclear labelling is observed in the septal-preoptic region, in the anterior hypothalamic area, and in the central hypothalamic area. Some estrogen-sensitive nuclear groups, such as lateral septum and hippocampus, do not show accumulation of radioactivity. In the uterus, luminal and glandular epithelium, stromal cells and muscle cells are labelled. A comparison of the quantitative nuclear uptake of radioactivity and of the different time intervals after the injection of different doses shows similar uptake of nuclear radioactivity. This is comparable to data obtained after [6,7-3H]estradiol ([3H]E2) injection. The results provide clear evidence for nuclear binding of catechol estrogens of the same magnitude as [3H]E2 after in vivo treatment.

Animals↗

Response properties of hypogastric afferent fibers supplying the uterus in the cat.

The present study was undertaken to examine the sensory function of uterine afferent fibers in cats at unknown stages of the estrous cycle. Single unit activity was recorded from strands of the hypogastric nerve of the anesthetized cat. Once a unit was found, the conduction velocity was determined and the mechanical receptive field localized on the uterus. The response properties of the unit to mechanical stimuli applied to the receptive field and to chemical stimuli applied by intra-arterial injection of algesic chemicals (bradykinin, KCl and capsaicin) into the uterine artery were studied. Single unit activity from a total of 52 units was examined in this study. Based on the conduction velocities, about 2/3 of these fibers were found to be unmyelinated C fibers and the remaining 1/3 were thinly myelinated A delta fibers. The receptive fields of most of these fibers were located at different parts of the uterine horn and body while a few were at the uterine cervix. Mechanical thresholds, as determined by von Frey filaments applied to the external surface of the uterus, varied more than 150-fold among mechanically sensitive units, ranging from extremely low to high thresholds. In addition, most of these afferents were activated by intra-arterially injected algesic chemicals, often by more than one chemical. The data in the present study suggest that a large portion of the cat uterus is innervated by the hypogastric nerve and that these afferents originate from sensory receptors that have potentially a wide range of functions. Their potential functions as low threshold mechanoreceptors and nociceptors are discussed.

Afferent Pathways↗

The effect of autonomic and psychotropic drugs on adrenaline reversal in the rat uterus.

Desipramine and other psychotropic and autonomic drugs were tested for their ability to prevent the motor response of the rat uterus to adrenaline in vitro. Those agents which have been shown to prevent catecholamine uptake into stores most readily reversed the motor response; those which had little or no effect on catecholamine storage were usually without effect on the motor response to adrenaline. The motor response of the rat uterus to adrenaline is due to prostaglandin E2. Agents blocking the motor response prevented the release of prostaglandin and did not block the action of prostaglandin on the uterus. Since all the effective agents also interfered with uptake with catecholamine stores it seems likely that passage of catecholamine in and out of storage depots is involved with the synthesis of prostaglandins.

Animals↗

Mechanism of action of histamine in the estrogen-primed rat uterus.

Histamine produced a dose-dependent relaxation of uterine strips obtained from the estrogen-primed rat uterus. The responses to histamine were blocked competitively by metiamide (10(-8)-10(-8) M), a specific H2-receptor antagonist. Propranolol, a selective beta-receptor blocker also produced competitive antagonism of the responses to histamine in the same dose range (10(-8)-10(-6) M). The pA2 value obtained for metiamide (8.9) was not significantly different from that obtained for propranolol (8.6). Nialamide (2.2 X 10(-6) M), the monoamine oxidase inhibitor, and cocaine (4.3 X 10(-6) M), the selective noradrenaline uptake blocker, potentiated the responses to histamine. However bretylium (2.4 X 10(-5) M), and adrenergic neuron blocker inhibited the responses to histamine. The combined effect of tyramine and histamine was found to be additive. Our data suggest that the histamine-induced relaxation of rat uterus may be produced through the stimulation of presynaptic H2-receptors which causes the release of noradrenaline. The released noradrenaline acts on the postsynaptic beta-receptors and produces relaxation of the rat uterus.

Animals↗

Cross tolerance between cromakalim and RP49356 in the uterus of the rat in vivo and in vitro.

We investigated tolerance to the potassium (K+) channel openers, cromakalim and RP49356 and cross tolerance between them in the uterus of the rat. Continuous infusion of RP49356 in vivo produced 5.2-fold (200 or 300 micrograms/kg per h) and 7.2-fold (600 micrograms/kg per h) desensitization of the uterus to RP49356. Uterine sensitivity to RP49356 was reduced 7.4-fold in cromakalim-tolerant rats and sensitivity to cromakalim was reduced 7.9-fold in RP49356-tolerant rats. Incubation of isolated uterus with 10 microM cromakalim for 4 h reduced uterine sensitivity to cromakalim by about 45-fold and to RP49356 by 2.1-fold but did not alter sensitivity to salbutamol. Incubation with 10 microM RP49356 for 4 h reduced sensitivity to RP49356 by 2.5-fold and to cromakalim by 3.8-fold. Occurrence of uterine tolerance to K+ channel openers in vitro suggests that tolerance in vivo has a pharmacodynamic basis. Cross tolerance between cromakalim and RP49356 provides evidence that these two K+ channel openers possess common binding sites and/or mechanism(s) of action. However, the greater extent of self-tolerance to cromakalim than to RP49356 suggests a difference in their actions.

Animals↗

Different regulation of the concentration of estrogen receptors in the rat liver and uterus following ovariectomy.

Data concerning the short- and longterm effects of ovariectomy on the levels of estrogen binding sites in the rat uterus and liver are presented. The information increases the understanding of the regulation of estrogen receptor synthesis. The circulating estrogen level is suggested to affect receptor synthesis in the uterus and liver differently. Shortly after gonadectomy (2--20 h), an elevation in the concentration of cytoplasmic binding sites in the uterus of 35% was observed, whereas no effect was seen in the liver cell. A longer period of time after ovariectomy (2--3 months) caused a reduction in the number of uterine receptor sites by 74%, whereas in the liver an increase of 84% was detected.

Animals↗

Caldesmon, a calmodulin-binding, F actin-interacting protein, is present in aorta, uterus and platelets.

Caldesmon, a protein originally found in chicken gizzard, was concluded also to be present in bovine aorta, uterus, and human platelets by demonstration of a protein with the following properties: (a) Ca2+-dependent calmodulin-binding; (b) binding to F actin in such way that the binding was broken on Ca2+-dependent binding of calmodulin; (c) cross-reactivity in immune blotting procedures with affinity-purified antibody against gizzard caldesmon; (d) similar subunit Mr-values on SDS-gel to those of gizzard caldesmon. Like gizzard caldesmon, platelet caldesmon was composed of two polypeptide bands of Mr 150 000 and 147 000, but caldesmon in aorta and uterus gave a single band of Mr 150 000. A polypeptide of Mr 165 000 that was immunologically distinct from caldesmon but, like caldesmon, bound to calmodulin and F actin in a flip-flop fashion, was also demonstrated in aorta and uterus.

Animals↗

Non-vascular transplantation of the rabbit uterus.

Transplantation of the uterus may be an optimal solution in young hysterectomized patients, in women with agenesis of the uterus or in severe uterine anomalies. In the human model, attempted tubal and ovarian homografts have usually failed. Eighteen rabbits underwent unilateral non-vascular uterine transplantation. Four rabbits underwent total unilateral uterine autograft. Three uteri showed severe inflammation and necrosis 72 h, 1 week and 1 month postoperatively. Thereafter, the operative technique was modified to avoid contamination from the vagina and four rabbits underwent supravaginal unilateral non-vascular autograft. Three uteri had preserved endometrial and myometrial structure on relaparotomy. The following four rabbits underwent homotransplantation of the uterus and showed acute rejection of the transplant. Under cyclosporine therapy three homotransplanted rabbits developed pelvic abscesses while three other rabbits showed preserved myometrial and endometrial structures.

Animals↗

Uterine motility in patients with bicornuate uterus.

This study analyzes uterine motility in 12 women with a bicornuate uterus using the results of the recordings of endo-uterine pressure, obtained with two balloon-closed catheters. Seven patients had symmetric uterine cavities, while the rest (5 patient) had very dissimilar ones. The registration of the uterine motility was carried out during various phases of the cycle and after the administration of two drugs (oxitocin and methylergobasine), with the following results: the bicornuate uterus has a spontaneous activity similar to that of a normal uterus. A similar contractile response was observed in the uteri with two anatomically symmetric horns, whereas a dissimilar response was typical of the uteri with marked anatomic differences between the two horns.

Catheterization↗