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Treatment of ectopic pregnancy with single-dose methotrexate in a patient with an intrauterine device. A case report.

BACKGROUND: Medical therapy for ectopic pregnancy is successful in 86-100% of selected patients. Patients who conceive with an intrauterine device (IUD) in place have an increased risk of ectopic pregnancy (30% of conceptions); these patients have been treated routinely by surgery. CASE: A 33-year-old woman at 7 weeks' gestation with a copper-containing IUD in place presented with an ectopic pregnancy based on transvaginal ultrasound, quantitative beta-human chorionic gonadotropin and physical examination findings. Because she desired to keep her IUD and avoid surgery, she was treated with intramuscular single-dose methotrexate. CONCLUSION: This case was the first reported successful medical treatment of an ectopic pregnancy in a patient with an IUD. There appeared to be no adverse clinical interactions between the methotrexate and IUD.

Adult↗

[Ectopic pregnancy: factors related to ovum anomalies?].

Identified risk factors for ectopic pregnancy (prior pelvic inflammatory disease, smoking at the time of conception, intrauterine device, obstetrical and surgical history) explain from 60 to 65% of the cases. Egg anomalies may also be a risk factor as it is likely that the transport of an abnormal egg along the uterine tube is less efficient than a normal one. We tested this hypothesis with data from two case-control studies with the same design covering a total of 1955 women. The risk of ectopic pregnancy increased specifically with age, which is compatible with our hypothesis. We also studied the associations with spontaneous abortion, considered to be a marker of the risk of pregnancies involving chromosomal malformations. We observed an association between ectopic pregnancy and spontaneous abortions (especially recurrent abortions), not explained by other known risk factors. Although our data do not supply a single definitive demonstration, our results converge to suggest that egg chromosomal anomalies may play a part in ectopic pregnancy aetiology.

Abortion, Spontaneous↗

Serum estradiol in the differential diagnosis of ectopic pregnancy.

In a prospective study using a cutoff value of 140 pg/mL, serum estradiol 17-beta assay had a sensitivity of 83% and a specificity of 100% in differentiating ectopic pregnancy (6 patients) from normal pregnancy with threatened abortion proceeding to viability (7 patients). In differentiating threatened abortion from spontaneous abortion (9 patients), the estradiol assay had a sensitivity of 88.9% and a specificity of 100%. All but one of the patients with ectopic pregnancy had estradiol levels below the cutoff value of 140 pg/mL, as did all but one of the patients who had spontaneous abortion. All the patients who had threatened abortion that progressed to viability had values well above the cutoff level. The mean estradiol values for the viable pregnancy group were significantly different from those of the other two groups. These data suggest that, at the institution where this study was done, serum estradiol determinations may be of value in the differentiation of both ectopic pregnancy and spontaneous abortion from threatened abortion but appears to be of very limited usefulness in distinguishing ectopic pregnancy from spontaneous abortion. The validity of these conclusions is limited by the small number of subjects. Further studies comprising greater numbers of subjects are needed.

Abortion, Spontaneous↗

[Single-dose intramuscular methotrexate for treatment of ectopic pregnancy].

OBJECTIVE: The efficacy and indication of single-dose intramuscular methotrexate to treat early ectopic pregnancy were explored. METHODS: 27 cases of ectopic pregnancy were treated by single-dose intramuscular methotrexate (50 mg/m2) without citrovorum rescue. The beta-hCG was monitored regularly till it became normal. Twelve of them recieved this regimen in outpatient service. RESULTS: 24 cases (88.9%) were successfully treated. Three failed and switched to operation. There were no significant differences (P > 0.05) in gestational age and size of adnexa ectopic mass between successful cases and failed cases, but highly significant differences (P < 0.01) in occurrence rate of abdominal pain and beta-hCG titers before treatment. CONCLUSION: The early diagnosis and adherence to strict criteria are the keys to successful management. No abdominal pain, ectopic mass < or = 5 cm in greatest dimension and titer of serum beta-hCG < 6000 IU/L were mainly indications of drug treatment.

Adult↗

Ultrasound studies in ectopic pregnancies.

Early diagnosis of ectopic pregnancy reduces the mortality and morbidity associated with the disease, and the morbidity associated with the therapy. When diagnosis was limited to the cases presenting with tubal rupture, salpingectomy was the only possible treatment. If ectopic pregnancy can be diagnosed earlier, clinicians are able to use new therapies such as laparoscopic microsurgery or medical therapy with methrotrexate, which are less invasive and less tissue destructive. Transvaginal ultrasound has proven to be an essential tool in the early diagnosis of ectopic pregnancy. Colour Doppler capacities further enhance the diagnostic sensitivity of transvaginal ultrasound for the early recognition of abnormal and normal intrauterine pregnancy, and small extrauterine masses. The aim of this paper is to provide an overview of the major sonographic signs and pitfalls in the ultrasound diagnosis of ectopic pregnancy.

Adnexa Uteri↗

Transvaginal color doppler ultrasound in the conservative treatment and surveillance of three ectopic pregnancies.

We evaluated the role of transvaginal color Doppler ultrasound in the treatment and follow-up after transvaginal instillation of methotrexate in ectopic pregnancy. Three patients diagnosed with ectopic pregnancies were treated with a single 50 mg dose of methotrexate, transvaginally instilled, under direct color sonographic guidance. Inclusion criteria required a gestational age of less than 8 weeks, non-ruptured ectopic pregnancy, gestational sac of less than 4 cm, and compliant patient. b-hCG titers, gestational sac sizes, and Doppler flow waveform analyses were followed at regular intervals. All three patients had falling b-hCG titers, shrinkage of the gestational sacs, and normalization of Doppler flow waveform indices. Transvaginal color Doppler ultrasound appears to be an effective adjunct in the treatment and follow-up of ectopic pregnancies treated with transvaginal instillation of methotrexate.

Abortifacient Agents↗

Chromosomal abnormalities in ectopic pregnancy chorionic villi.

OBJECTIVE: To evaluate the incidence of chromosomal abnormalities in ectopic pregnancy chorionic villi. METHODS: A prospective study of patients with the diagnosis of ectopic pregnancy was conducted, with chorionic villi obtained at the time of surgical therapy cultured and analyzed for karyotype. Review of the patient's medical record and ultrasound evaluation was then completed and findings correlated with karyotype results. RESULTS: Twenty-two patients undergoing surgery for the diagnosis of ectopic pregnancy yielded chorionic villi for culture. Successful culture was performed in 21 patients, with 3 (14%) revealing abnormal karyotypes. Review of the medical record showed ultrasound results consistent with fetal development or a gestational sac in 15 of 18 patients with normal chromosomal analysis. Three of 6 patients without fetal development yielded abnormal chromosomal findings. CONCLUSION: Our results confirm that a high degree of success can be achieved in the karyotype analysis of ectopic pregnancy chorionic villi and that these conceptuses have a rate of abnormality similar to that reported for intrauterine gestations. Our data further suggest that when a gestational sac or fetal pole is identified by ultrasound, there is usually a normal karyotype.

Chorionic Gonadotropin, beta Subunit, Human↗

Ectopic expression of the ErbB-3 binding protein ebp1 inhibits growth and induces differentiation of human breast cancer cell lines.

Ebp1, an ErbB-3 binding protein, translocates from the cytoplasm to the nucleus of human breast cancer cells after treatment with the ErbB-3 ligand, heregulin. The purpose of these studies was to examine the effects of ectopic expression of ebp1 on the biological properties of human ErbB-3-expressing breast carcinoma cell lines. Ectopic expression of ebp1 in ErbB-2, ErbB-3-expressing breast carcinoma cell lines resulted in inhibition of colony formation, a decreased proliferation rate, an accumulation of cells in the G2/M phase of the cell cycle, and suppression of growth in soft agar. Ectopic expression of ebp1 led to a more differentiated phenotype in AU565 breast cancer cells, as evidenced by increased expression of lipid droplets and of the milk protein casein. Basal phosphorylation of extracellular regulated kinases (Erks) 1 and 2, kinases activated by heregulin treatment, was also observed in ebp1 transfectants. The promoter for the intercellular adhesion molecule-1 gene, a heregulin-inducible gene, was constitutively activated in ebp1 transfectants as determined by reporter construct analysis. These data demonstrate that ectopic expression of the ErbB-3 binding protein Ebp1 inhibits proliferation and induces differentiation of ErbB-2, ErbB-3-expressing human breast carcinoma cell lines.

Breast Neoplasms↗

Acinic cell carcinoma arising in ectopic salivary gland tissue.

Two cases of a rare entity, acinic cell carcinomas, which apparently arose primarily from ectopic salivary gland tissue, are presented. Salivary gland ducts and acini frequently may be found incorporated within intraparotid lymph nodes and less commonly within extraglandular cervical nodes. Ectopic salivary glands may also be seen, although rarely, elsewhere in the head and neck area. The most common tumor to arise from intranodal salivary gland tissue is papillary cystadenoma lymphomatosum; however, other salivary gland-type neoplasms rarely may do so. In our cases, one tumor apparently originated primarily within a paraparotid lymph node and the other in the lateral mid- to low-neck area. Neither of our patients had a demonstrable lesion of a major or minor salivary gland; thus their tumors are presumed to have originated primarily from ectopic salivary gland tissue. The clinician and the pathologist should consider the possibility of a neoplasm arising in ectopic tissue when a salivary gland type tumor is identified away from sites where major and minor salivary glands normally are found.

Adolescent↗

Recurrent acromegaly resulting from ectopic growth hormone gene expression by a metastatic pancreatic tumor.

BACKGROUND: Acromegaly is usually the result of a pituitary growth hormone (GH)-cell adenoma or is more rarely due to ectopic secretion of GH-releasing hormone (GHRH). The authors previously described a more unusual form of acromegaly secondary to ectopic GH synthesis by a pancreatic islet cell tumor. METHODS: One year after tumor resection and transient disease remission, multiple abdominal metastases were identified with accompanying elevated levels of circulating GH and insulin-like growth factor-1 (IGF-1). Serial 24-hour GH sampling was performed before and after intravenous GHRH or thyrotropin releasing hormone (TRH) administration during treatment with bromocriptine; treatment with the somatostatin (SRIF) analogue octreotide; or no treatment. RNA from abdominal tumor tissue was extracted and subjected to Northern gel electrophoresis and GH hybridization analysis. RESULTS: Neither GHRH nor TRH resulted in stimulation of the elevated GH levels. Bromocriptine and octreotide did not suppress GH secretion but attenuated the thyroid stimulating hormone (TSH) response to TRH administration. Octreotide (as much as 1500 micrograms/d) was clinically, biochemically, and radiographically ineffective. GH-secreting abdominal tumor tissue expressed a 0.9-kb mRNA transcript consistent with the size of authentic human GH mRNA. CONCLUSION: The natural history and ectopic nature of a GH-producing pancreatic carcinoma has been documented, with biochemical remission occurring after initial tumor resection, with autonomous GH hypersecretion after tumor recurrence, and with RNA analysis demonstrating ectopic activation of GH gene transcription.

Acromegaly↗

Germinal cell ectopism in the strepsirhine prosimian Galago crassicaudatus crassicaudatus.

The presence of germinal cells outside of the embryonal and fetal gonads of the strepsirhine prosimian Galago crassicaudatus crassicaudatus is described. Forty-three embryos and fetuses from day 26 or 27 of gestational age to near term were studied: more than 90% possessed germinal cells in ectopic sites situated either far from (extragonadal ectopism) or close to the gonads (perigonadal ectopism). The first sites were the walls of the aorta and mesenteric artery, the stroma between the aorta and the cardinal vein, and the retroperitoneal neuroganglia. The second were the mesenchyme dorsal to the gonads and around the vestigia of the mesonephric glomeruli and tubules, and the rete ovarii and testis. The ectopic cells were generally present in conscpicuous numbers, in some animals being more numerous than in the gonads. Those situated far from the gonads underwent degeneration and decreased significantly in numbers during post-embryonal stages of development, while the others remained numerous and functionally active up to near term. While the differentiation of the extragonadal germinal cells after day 60 of gestational age could not be studied due to technical difficulties, the XX and XY cells in perigonadal sites appeared to follow patterns of differentiation identical to those of their entopic counterparts.

Animals↗

Formation of ectopic neurepithelium in chick blastoderms: age-related capacities for induction and self-differentiation following transplantation of quail Hensen's nodes.

Hensen's node, regarded as the avian and mammalian homologue of Spemann's neural inducer (i.e., the amphibian dorsal blastoporal lip), has been transplanted in many previous studies to the germinal crescent of avian blastoderms to examine ectopic neural induction. All these studies have suffered from one or more major shortcomings, the most significant of which has been the lack of a reliable cell marker to determine the contributions of graft cells to ectopic embryos. In the absence of such marker, induced (i.e., derived from the host) and self-differentiated (i.e., derived from the graft) neurepithelium cannot be distinguished from one another with certainty. We have transplanted quail Hensen's nodes to chick host blastoderms and have subsequently used the quail nucleolar heterochromatin marker to identify graft cells unequivocally. We systematically varied both donor and host ages (i.e., stages 3-8 and 3-5, respectively) to examine the effects of age on ectopic neural induction and self-differentiation. Our results demonstrate that the age of the donor is more critical than that of the host over the stages examined. With advancing donor age, the frequency of host induction decreases, while the frequency of graft self-differentiation increases. Previous studies not using cell markers have concluded that the craniocaudal level of the induced neuraxis is determined by the age of the donor, that is, young donors induce cranial neuraxial levels, whereas old donors induce caudal levels. By contrast, we found that with grafts from older donors, neurepithelium was more commonly self-differentiated rather than induced and that progressively more caudal levels of the neuraxis self-differentiated with advancing donor age. Induction of caudal neuraxial levels never occurred in the absence of induced cranial levels. The frequency of neural induction was inversely correlated with the age of the donor and directly correlated with the quantity of graft endodermal cells contributed to the ectopic embryo, supporting a previous assertion that in avian embryos, the earliest and principal source of neural inducer lies within the endoderm rather than mesoderm. From our results, we propose that the role of neural induction is to produce neurepithelium of unspecified regional character, and that the formation of regional character depends on subsequent morphogenetic events.

Age Factors↗

Fine-needle aspiration cytology of a primary ectopic meningioma.

Meningiomas are benign tumors derived from arachnoid cells. Most commonly an intracranial lesion, meningiomas may be found extracranially in various anatomic sites. A 23-yr-old white female presented with left-sided palpable mass located submucosally in the floor of the mouth. CT scan revealed no evidence of mass elsewhere in the head and neck region. Fine-needle aspiration cytology (FNAC) showed loose and cohesive cellular fragments with lobular growth pattern and uniform round or ovoid cells. The diagnosis of low-grade salivary gland neoplasm, not further classified, was made. The tumor was locally excised. The differential diagnoses of an extracranial meningioma and pleomorphic adenoma were discussed at the frozen section. Based on light microscopic, immunohistochemical, and electron microscopic (EM) findings, the final diagnosis of an ectopic meningioma was rendered. Ectopic meningiomas may pose a diagnostic challenge to clinicians and cytopathologists. It is easily forgotten in the list of differential diagnosis at an ectopic site. Primary ectopic meningioma in a region containing salivary gland(s) may mimic benign and low-grade malignant salivary gland tumors in FNAC.

Adenoma↗

Six3 promotes the formation of ectopic optic vesicle-like structures in mouse embryos.

A few years ago, three novel murine homeobox genes closely related to the Drosophila sine oculis (so) gene (Six1-3) were isolated and were all included in the Six/so gene family. Because of its early expression in the developing eye field, Six3 was initially thought to be the functional ortholog of the Drosophila so gene. This hypothesis was further supported by the demonstration that ectopic Six3 expression in medaka fish (Oryzias latipes) promotes the formation of ectopic lens and retina tissue. Here, we show that similar to Drosophila, where the eyeless/Pax6 gene regulates the eye-specific expression of so, Six3 expression in the murine lens placodal ectoderm is also controlled by Pax6. We also show that ectopic Six3 expression promotes the formation of ectopic optic vesicle-like structures in the hindbrain-midbrain region of developing mouse embryos.

Amino Acid Sequence↗

Ectopic expression of the homeobox gene Cux-1 rescues calcineurin inhibition in mouse embryonic kidney cultures.

Cux-1 is a murine homeobox gene structurally related to Drosophila cut. Cux-1 is highly expressed in the nephrogenic zone of the developing kidney, where its expression coincides with cell proliferation. Cux-1 functions as a transcriptional repressor of the cyclin kinase inhibitors (CKI) p21 and p27. Cux-1 DNA binding activity is negatively regulated by phosphorylation, and dephosphorylation of Cux-1 results in increased DNA binding. Transgenic mice ectopically expressing Cux-1 develop renal hyperplasia associated with the down-regulation of the CKI p27. Calcineurin A (CnA) alpha (-/-) mice display renal hypoplasia associated with the ectopic expression of p27. CnA is a serine/threonine phosphatase activated by intracellular calcium. Inhibiting CnA with cyclosporin A (CsA) leads to nephron deficit in rat metanephric organ cultures and apoptosis in various renal cell lines. To determine whether the ectopic expression of p27 in CnA-alpha -/- kidneys results from the down-regulation of Cux-1, metanephroi from embryonic Cux-1 transgenic and wild-type mice were harvested and cultured with CsA for 5 days. CsA treatment significantly inhibited growth of wild-type metanephroi. In contrast, CsA-treated Cux-1 transgenic kidney cultures were not growth inhibited, but showed high levels of cell proliferation in the nephrogenic zone. Moreover, in CsA-treated Cux-1 transgenic kidney cultures, p27 was not expressed in the nephrogenic zone, but only up-regulated in maturing glomeruli and tubules. Taken together, our results demonstrate that ectopic expression of Cux-1 can rescue the effects of CsA inhibition of CnA and suggest that Cux-1 may be regulated by calcineurin A.

Animals↗

Ectopic sequences from truncated HMGIC in liposarcomas are derived from various amplified chromosomal regions.

The HMGIC gene codes for an architectural transcription factor frequently rearranged by translocation in lipomas and other benign mesenchymal tumors. In sarcomas, malignant tumors of mesenchymal origin, the gene is also found to be rearranged, but in addition amplified and overexpressed. Here we report the sequence, chromosomal localization, and expression patterns of 11 novel ectopic sequences fused to exons 2 and 3 of HMGIC in seven different sarcoma samples. In addition, we identified a number of variant transcripts observed previously in benign tumors. Consistent with the suggested role of HMGIC in adipocytic differentiation, most of the novel ectopic sequences were observed in well-differentiated liposarcomas. These tumors are known to have complex marker chromosomes containing amplified segments from several chromosomes. Five novel sequences were derived from 12q14-q15, where HMGIC resides, two from 1q24, a region frequently amplified in these types of tumors, two from 11q14, and one from chromosome 2. All except one of the aberrant transcripts encoded truncated proteins with intact DNA-binding domains (AT hooks) but lacking the C-terminal acidic region, a target for constitutive phosphorylation by protein kinase CK2. Some of the ectopic sequences were transcribed in other tissues, and most of the ectopic sequences also showed recurrent amplification in liposarcomas.

Amino Acid Sequence↗

Propensity of ectopic liver to hepatocarcinogenesis: case reports and a review of the literature.

Two patients with ectopic liver are described. In one patient, a small ectopic liver attached to the gastric serosa developed hepatocellular carcinoma (HCC). The preoperative diagnosis was an alpha-fetoprotein (AFP)-producing carcinoma and a malignant ulcer of the stomach. Total gastrectomy and esophago-jejunostomy were performed. The tumor that measured 4 x 2 x 2 cm contained an AFP-producing HCC and normal liver tissue. In another patient who had alcoholic cirrhosis, ectopic liver on the serosa of the gallbladder was found to have the same histological changes as the mother liver. A survey of the literature disclosed more than 20 cases in which HCC developed outside the liver; the liver did not have HCC. By contrast, there was only one report on HCC occurring in the liver in the presence of a noncancerous, relatively large accessory liver lobe. Because ectopic liver does not have a complete vascular and ductal system as a normal liver, it is perhaps functionally handicapped and more prone to hepatocarcinogenesis.

Carcinoma, Hepatocellular↗

Prolonged ectopic calcification induced by BMP-2-derived synthetic peptide.

Bone morphogenetic protein-2 (BMP-2) promotes the formation and regeneration of bone and cartilage, and therefore constitutes the most promising candidate for a bone repair material. However, it also has a wide range of functions, such as in organogenesis and apoptosis. Therefore, we investigated a novel synthetic peptide corresponding to residues 73-92 of BMP-2. This peptide bound to a BMP-2-specific receptor and elevated both alkaline phosphatase activity and osteocalcin mRNA in the murine cell line, C3H10T1/2. The 73-92 peptide also induced ectopic calcification when conjugated to a covalently crosslinked alginate gel. Here we report that the 73-92 peptide-conjugated alginate gel showed prolonged ectopic calcification for up to 7 weeks in rat calf muscle. In contrast, rhBMP-2-impregnated collagen gel showed maximum ectopic calcification at 3 weeks, and the calcified products that had formed disappeared after 5 weeks. Histological examination showed that the 73-92 peptide-conjugated alginate gel induced many osteoblast-like cells and few osteoclasts. In contrast, rhBMP-2-impregnated collagen gel induced many osteoclasts. These results suggest that the 73-92 peptide on alginate gel remains active at the implanted site, continuously induces differentiation of osteoblast precursor cells into osteoblasts, and activates osteoblasts to promote ectopic calcification.

Alginates↗