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[Integrin expression in eutopic and ectopic endometrium].

The significance of retrograde menstruation as a risk factor for endometriosis has been confirmed by numerous clinical observations. Integrins mediate both cell-cell and cell-matrix adhesion, and it is therefore suspected that integrins are involved in the development of endometriosis. Using immunohistochemistry, integrin expression in eutopic and ectopic endometrium is examined in endometriosis patients and control individuals. In nearly all cases, the glandular epithelial cells in the endometrium showed expression of alpha (2-), alpha (3)-, alpha (6)- and alpha (v)- integrin and a low percentage of expression of alpha (1)-, alpha (4)-, and alpha (5)-integrin. In comparison with eutopic endometrium, ectopic endometrium shows reduced expression of alpha (2)- and alpha (v)-integrin. Since no differences in alpha (2)- and alpha (v)-integrin expression were observed in eutopic endometrium between endometriosis patients and control individuals, it may be suspected that the reduced expression of these in ectopic endometrium is explained by influences in the altered environment -- e. g., in the peritoneal fluid -- on the ectopic endometrium.

Biopsy↗

Predictors of success of methotrexate treatment in women with tubal ectopic pregnancies.

BACKGROUND: The use of methotrexate for the treatment of women with tubal ectopic pregnancies is now common practice. However, the clinical and hormonal determinants of the success of this treatment are not known. METHODS: We studied 350 women with tubal ectopic pregnancies who were treated with methotrexate intramuscularly according to a single-dose protocol. Pretreatment serum concentrations of human chorionic gonadotropin and progesterone, the size and volume of the gestational mass, fetal cardiac activity, and the presence of fluid (presumably blood) in the peritoneal cavity were correlated with the efficacy of therapy, as defined by resolution of the ectopic pregnancy without the need for surgical intervention. RESULTS: There was no relation between the women's age or parity, the size or volume of the conceptus, or the presence of fluid in the peritoneal cavity and the efficacy of treatment. Among the 320 women in whom treatment was successful (91 percent), the mean (+/-SD) serum chorionic gonadotropin and progesterone concentrations were 4019+/-6362 mIU per milliliter and 6.9+/-6.7 ng per milliliter (21.9+/-21.3 nmol per liter), respectively, as compared with 13,420+/-16,590 mIU per milliliter and 10.2+/-5.5 ng per milliliter (32.4+/-17.5 nmol per liter) (P<0.001 and P=0.02) in the 30 women in whom treatment was not successful. Fetal cardiac activity was present in 12 percent of the successfully treated cases and 30 percent of those in which treatment was not successful (P=0.01). Regression analysis revealed the pretreatment serum chorionic gonadotropin concentration to be the only factor that contributed to the failure rate. CONCLUSIONS: Among women with tubal ectopic pregnancies, a high serum chorionic gonadotropin concentration is the most important factor associated with failure of treatment with a single-dose methotrexate protocol.

Adult↗

Ectopic opening of the common bile duct in the duodenal bulb: clinical implications.

BACKGROUND: An ectopic opening of the common bile duct in the duodenal bulb is extremely rare, and the clinical significance of this anomaly has not been clarified. This study analyzed the clinical implications and cholangiographic findings of this anomaly. METHODS: A total of 18 patients (15 men, 3 women; median age, 51 years) with an ectopic opening of the common bile duct in the duodenal bulb were studied. Medical records, endoscopic findings, and cholangiographic and other radiographic findings were reviewed. RESULTS: All 18 patients had biliary pain; 7 had fever and chills. Fifteen (83%) had diffuse dilatation of the extrahepatic bile ducts with or without intrahepatic bile duct dilation. Associated bile duct stones were found in 10 (56%) patients. The papilla in the bulb had an orifice stained with bile at endoscopy, which was associated with duodenal ulcer disease found in 13 (72%) patients. The distal end of the common bile duct was tapered and narrowed and had a hook shape in all patients. CONCLUSION: An ectopic opening of the common bile duct in the duodenal bulb may be associated with clinical entities such as recurrent or intractable duodenal ulcer, choledocholithiasis, or acute cholangitis. Although these openings are rare, knowledge of the endoscopic and radiographic findings of an ectopic opening of the common bile duct in the duodenal bulb may help to clarify the cause of chronic recurrent duodenal ulcer disease in some patients and prevent damage to the bile duct during surgery.

Adult↗

Innervation of ectopic endometrium in a rat model of endometriosis.

Endometriosis (ENDO) is a disorder in which vascularized growths of endometrial tissue occur outside the uterus. Its symptoms include reduced fertility and severe pelvic pain. Mechanisms that maintain the ectopic growths and evoke symptoms are poorly understood. One factor not yet considered is that the ectopic growths develop their own innervation. Here, we tested the hypothesis that the growths develop both an autonomic and a sensory innervation. We used a rat model of surgically induced ENDO whose growths mimic those in women. Furthermore, similar to women with ENDO, such rats exhibit reduced fertility and increased pelvic nociception. The ENDO was induced by autotransplanting, on mesenteric cascade arteries, small pieces of uterus that formed vascularized cysts. The cysts and healthy uterus were harvested from proestrous rats and immunostained using the pan-neuronal marker PGP9.5 and specific markers for calcitonin gene-related peptide (CGRP) (sensory C and A delta fibers), substance P (SP) (sensory C and A delta fibers) and vesicular monoamine transporter (sympathetic fibers). Cysts (like the uterus) were robustly innervated, with many PGP9.5-stained neurites accompanying blood vessels and extending into nearby luminal epithelial layers. CGRP-, SP-, and vesicular monoamine transporter-immunostained neurites also were observed, with CGRP and SP neurites extending the furthest into the cyst lining. These results demonstrate that ectopic endometrial growths develop an autonomic and sensory innervation. This innervation could contribute not only to symptoms associated with ENDO but also to maintenance of the ectopic growths.

Animals↗

Ectopic scute induces Drosophila ommatidia development without R8 founder photoreceptors.

During development of the Drosophila peripheral nervous system, different proneural genes encoding basic helix-loop-helix transcription factors are required for different sensory organs to form. atonal (ato) is the proneural gene required for chordotonal organs and R8 photoreceptors, whereas the achaete-scute complex contains proneural genes for external sensory organs such as the macrochaetae, large sensory bristles. Whereas ectopic ato expression induces chordotonal organ formation, ectopic scute expression produces external sensory organs but not chordotonal organs in the wing. Proneural genes thus appear to specify the sensory organ type. In the ommatidium, or unit eye, R8 is the first photoreceptor to form and appears to recruit other photoreceptors and support cells. In the atonal(1) (ato(1)) mutant, R8 photoreceptors fail to form, thereby resulting in the complete absence of ommatidia. To our surprise, we found that ectopic scute expression in the ato(1) mutant induces the formation of ommatidia, which occasionally sprout ectopic macrochaetae. Remarkably, many scute-induced ommatidia lack R8 although they contain outer photoreceptors.

Animals↗

Bone patterning is altered in the regenerating zebrafish caudal fin after ectopic expression of sonic hedgehog and bmp2b or exposure to cyclopamine.

Amputation of the zebrafish caudal fin stimulates regeneration of the dermal skeleton and reexpression of sonic hedgehog (shh)-signaling pathway genes. Expression patterns suggest a role for shh signaling in the secretion and patterning of the regenerating dermal bone, but a direct role has not been demonstrated. We established an in vivo method of gene transfection to express ectopically genes in the blastema of regenerating fins. Ectopic expression of shh or bmp2 in the blastema-induced excess bone deposition and altered patterning of the regenerate. The effects of shh ectopic expression could be antagonized by ectopic expression of chordin, an inhibitor of bone morphogenetic protein (bmp) signaling. We disrupted shh signaling in the regenerating fin by exposure to cyclopamine and found a dose-dependent inhibition of fin outgrowth, accumulation of melanocytes in the distal region of each fin ray, loss of actinotrichia, and reduction in cell proliferation in the mesenchyme. Morphological changes were accompanied by an expansion, followed by a reduction, in domains of shh expression and a rapid abolition of ptc1 expression. These results implicate shh and bmp2b signaling in the proliferation and/or differentiation of specialized bone-secreting cells in the blastema and suggest shh expression may be controlled by regulatory feedback mechanisms that define the region of bone secretion in the outgrowing fin.

Animals↗

Retrotransposition of a yeast group II intron occurs by reverse splicing directly into ectopic DNA sites.

Group II introns, the presumed ancestors of nuclear pre-mRNA introns, are site-specific retroelements. In addition to "homing" to unoccupied sites in intronless alleles, group II introns transpose at low frequency to ectopic sites that resemble the normal homing site. Two general mechanisms have been proposed for group II intron transposition, one involving reverse splicing of the intron RNA directly into an ectopic DNA site, and the other involving reverse splicing into a site in RNA followed by reverse transcription and integration of the resulting cDNA by homologous recombination. Here, by using an "inverted-site" strategy, we show that the yeast mtDNA group II intron aI1 retrotransposes by reverse splicing directly into an ectopic DNA site. This same mechanism could account for other previously described ectopic transposition events in fungi and bacteria and may have contributed to the dispersal of group II introns into different genes.

Base Sequence↗

Hereditary ectopic salivary gland: survey of three generations.

An ectopic salivary gland is different from a branchial cleft fistula, which generally results from heteroplasia within the remnants of the second branchial cleft. Compared to a branchial cleft fistula, surgery for an ectopic salivary gland is relatively simple. This study describes five generations of a family with typical clinical features of ectopic salivary gland in the neck. This study is the first to report the rare familial occurrence of ectopic cervical salivary gland and discuss its imaging results, surgical management, and histopathology.

Adult↗

Laparoscopic management of ectopic pregnancy: a 5-year experience.

The objective of this study was to review our management of ectopic pregnancy with the introduction of a laparoscopic service to the obstetrics and gynaecology department at South Cleveland Hospital. A retrospective analysis of 210 cases of ectopic pregnancy managed from May 1995 to May 2000 including operative findings and surgical data were collected prospectively over the past 5 years. All our women with an ectopic pregnancy were treated surgically. One hundred and seventy-seven (84.3%) patients were managed successfully laparoscopically with no major intraoperative or postoperative complications. Thirty-three (15.7%) women were managed by laparotomy for various reasons. Salpingectomy was the main (80%) procedure performed either by laparoscopy or by laparotomy. Thirty-five (16.7%) women were treated conservatively by salpingostomy. Of these 22.9% achieved a successful pregnancy and delivery. Half of our patients were managed by senior registrars. The estimated blood loss, the need for blood transfusion and the length of hospital stay following laparoscopic treatment were significantly less than those in laparotomy group. This study demonstrated that laparoscopic management of ectopic pregnancy is the most beneficial procedure with maximum safety and efficiency when the laparoscopic service is added to the unit.

Adult↗

Morbidity and mortality following tubal ectopic pregnancies in Enugu, Nigeria.

Our objective was to determine the current incidence, clinical pattern, surgical and medical management, maternal morbidity and mortality from tubal pregnancies in Enugu, Nigeria. The records of all patients treated for tubal pregnancy at the University of Nigeria Teaching Hospital, Enugu from 1 January 1997 to 31 December 2003 were reviewed. The number of tubal ectopic pregnancies was 136, while the total number of hospital deliveries was 6,003 giving a ratio of 1:44. There were four maternal deaths due to tubal pregnancy, out of a total of 126 maternal deaths that occurred during the same period. Ectopic pregnancy was prevalent in young single women with a previous history of induced abortion and resultant pelvic infection. The most common mode of treatment is salpingectomy. Most gynaecologists are not competent in operative laparoscopy and often do not use medical management of ectopic pregnancy. However, late presentation with haemoperitoneum limits the use of conservative treatment. Maternal morbidity and mortality due to tubal pregnancy is rising in Enugu, Nigeria. Preventive efforts should aim at health education and liberal contraceptive utilisation. Provision of more sophisticated equipment and tests in the management of ectopic pregnancies may in the long term be economically viable. Currently, autotransfusion is under utilised.

Adolescent↗

In situ gene expression analysis during BMP2-induced ectopic bone formation in mice shows simultaneous endochondral and intramembranous ossification.

We examined the molecular progression of ectopic bone development upon application of recombinant human bone morphogenetic protein-2 (rhBMP2), using a commercial collagen type I carrier, in the hind quarter muscles of mice. We performed a gene expression study using mRNA in situ hybridisation to compare embryonic cartilage and bone formation with BMP2-induced ectopic bone formation. As bone growth can be induced postnatally or in adult animals, we examined the expression of molecules regulating embryonic bone development. We found that the mRNAs of the same molecules, such as Indian hedgehog (IHH), parathyroid hormone (PTH)/PTH-related peptide receptor (PPR) and BMPs, that regulate embryonic cartilage and bone development, are expressed during BMP-induced ectopic bone formation, suggesting parallels in the mechanisms controlling these processes. Our studies support by molecular means the previous findings in rats that BMP2-induced ectopic bone formation in mice undergoes bone development involving both modes, endochondral and intramembranous ossification, simultaneously at different sites of the implant.

Animals↗

Operative laparoscopy in the management of tubal ectopic pregnancy.

One hundred and seventeen consecutive patients with diagnosis of ectopic pregnancy admitted to Temple University Hospital between October 1989 and March 1992 were divided into two groups. Group 1 consisted of 56 patients with operative laparoscopy and Group 2 consisted of 61 patients treated by laparotomy. The two groups were similar for age, race, parity, gestation, presentation, and location of the ectopic gestations. Fifty seven percent of patients in the laparoscopy group were treated by salpingectomy and 43% by salpingostomy, compared to 84% and 16% respectively in the laparotomy group. Mean operative time for laparoscopy was 58 min and 42 min for laparotomy. Complication rates were similar in the two sub-groups. Only two patients in the laparoscopy group required subsequent laparotomy, one to assure hemostasis and one, 5 weeks following surgery, for persistent trophoblastic disease. Operative laparoscopy was associated with a significantly shorter length of hospital stay (1.25 v. 4.39 days). This reflected in a lower cost of hospital stay ($10,105 vs. $13,608). The present data demonstrates that operative laparoscopy is not only safe and effective, but also more economical than open laparotomy in the treatment of ectopic pregnancies. This procedure is expected to replace laparotomy for the treatment of most cases of tubal ectopic pregnancy.

Adolescent↗

Controversial ectopic thyroid: a case report of thyroid tissue in the axilla and benign total thyroidectomy.

A 43-year-old woman presented with a mass in her left axilla, which was surgically excised. Histologically, the tissue was a reactive lymph node with adjacent thyroid follicular tissue. The differential diagnosis included benign ectopic thyroid versus metastatic well-differentiated follicular-derived thyroid carcinoma. Because of the possibility of carcinoma, the patient underwent a diagnostic total thyroidectomy. The thyroid was grossly normal with no histologic evidence of malignancy. Post-operatively, the patient underwent a whole body 131I scan. Aside from an expected residual uptake in the thyroid bed region, there was no extrathyroidal uptake to suggest additional ectopic thyroid tissue or metastatic disease. At the time of this scan, her thyrotropin (TSH) was 92.8 microU/mL, thyroglobulin was less than 0.3 ng/mL, and thyroglobulin antibody was less than 3 IU/mL. Abnormalities in the embryologic development and migration of the thyroid gland can result in ectopic thyroid tissue. The most frequent locations are along the midline from the base of the tongue to the mediastinum. Only rare case reports exist of ectopic thyroid in other locations, including the chest (heart, trachea), abdomen (liver, gallbladder, pancreas), and pelvis (vagina). This case represents the first description of thyroid tissue in the axilla with a histologically benign thyroid gland.

Adult↗

Ectopic intratracheal thyroid: an illustrative case report and literature review.

A 19-year-old woman was treated with bronchodilators for new-onset dyspnea with exercise. Her symptoms progressively worsened, culminating 4 months later in acute shortness of breath at rest. Flow-volume loops suggested a fixed obstruction and a computed tomography scan of the neck revealed a large subglottic mass. The patient underwent emergent tracheostomy and laryngoscopy and a near-obstructing intratracheal mass was found. Biopsy showed ectopic thyroid tissue. Magnetic resonance imaging of the neck showed a 1.4-cm tracheal lesion and a normally located thyroid gland. The intratracheal mass was resected endoscopically. Pathology revealed hyperplastic ectopic thyroid tissue. The patient has been maintained on thyroid hormone suppression therapy for 2 years without growth of the residual intratracheal thyroid tissue. She recently underwent a surgical palate expansion. We present this case, along with a literature review of ectopic intratracheal thyroid, its epidemiology, possible etiologies, genetic underpinnings, presentation, and treatment. The co-occurrence of an ectopic thyroid, a functioning orthotopic gland, and a high arched palate is also discussed.

Adult↗

A 4-wk high-fructose diet alters lipid metabolism without affecting insulin sensitivity or ectopic lipids in healthy humans.

BACKGROUND: High fructose consumption is suspected to be causally linked to the epidemics of obesity and metabolic disorders. In rodents, fructose leads to insulin resistance and ectopic lipid deposition. In humans, the effects of fructose on insulin sensitivity remain debated, whereas its effect on ectopic lipids has never been investigated. OBJECTIVE: We assessed the effect of moderate fructose supplementation on insulin sensitivity (IS) and ectopic lipids in healthy male volunteers (n = 7). DESIGN: IS, intrahepatocellular lipids (IHCL), and intramyocellular lipids (IMCL) were measured before and after 1 and 4 wk of a high-fructose diet containing 1.5 g fructose . kg body wt(-1) . d(-1). Adipose tissue IS was evaluated from nonesterified fatty acid suppression, hepatic IS from suppression of hepatic glucose output (6,6-2H2-glucose), and muscle IS from the whole-body glucose disposal rate during a 2-step hyperinsulinemic euglycemic clamp. IHCL and IMCL were measured by 1H magnetic resonance spectroscopy. RESULTS: Fructose caused significant (P < 0.05) increases in fasting plasma concentrations of triacylglycerol (36%), VLDL-triacylglycerol (72%), lactate (49%), glucose (5.5%), and leptin (48%) without any significant changes in body weight, IHCL, IMCL, or IS. IHCL were negatively correlated with triacylglycerol after 4 wk of the high-fructose diet (r = -0.78, P < 0.05). CONCLUSION: Moderate fructose supplementation over 4 wk increases plasma triacylglycerol and glucose concentrations without causing ectopic lipid deposition or insulin resistance in healthy humans.

Adult↗

Prevalence of ectopic ventricular activity after left ventricular mass regression.

To assess the effects of left ventricular mass reduction on the prevalence of ventricular ectopic activity, we conducted a double-blind, placebo-controlled trial measuring ambulatory 48 h premature ventricular depolarizations in 27 patients with mild-to-moderate hypertension and an increased left ventricular mass index. Data was obtained at baseline and 6 +/- 2 months after randomization to either 25 mg captopril or placebo twice a day. Patients on captopril attained reduction in blood pressure from 167 +/- 11/103 +/- 6 to 136 +/- 10/85 +/- 5 mm Hg (P = .001), left ventricular mass index regression from 149 +/- 17 to 96 +/- 23 g/m2 (P = .001), and ventricular ectopic activity reduction from 413 +/- 172 to 77 +/- 27 ventricular extrasystoles/day (P = .001). Patients on placebo had no significant change in blood pressure (from 162 +/- 11/101 +/- 6 at baseline to 160 +/- 8/100 +/- 8 mm Hg after 6 months; P = NS). In the placebo group left ventricular mass index increased from 155 +/- 40 to 182 +/- 51 g/m2 (P = .01), and ventricular ectopic activity decreased from 634 +/- 293 to 562 +/- 260 ventricular extrasystoles/day (P = NS). Eight out of 14 patients on captopril (57%) and 1 out of 13 patients on placebo (8%) achieved reduction > 85% in ventricular ectopic activity per day (P = .004). Using multivariate logistic regression analysis, left ventricular mass index regression and reduction in systolic blood pressure were the most important correlates for this effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Captopril↗

A mechanism for ectopic firing in central demyelinated axons.

Intracellular recordings of ectopic activity were made from demyelinated axons in rat dorsal columns using in vitro techniques. On-going bursts of discharges were observed in some axons, and these were sometimes superimposed upon slow depolarizing potentials. These intracellularly recorded, depolarizing potentials were strongly reminiscent of the slow negative potentials previously recorded extracellularly from the periaxonal region of normal myelinated fibres following potassium loading of this space. Also, in previously silent demyelinated axons, ectopic activity could sometimes be induced by brief periods of high frequency stimulation applied remotely from the lesion. The generation of the ectopic activity can be explained in terms of an artificially increased periaxonal concentration of potassium which may lead to the opening of internodal potassium channels and an inward potassium current. We suggest that a raised periaxonal potassium concentration may occur within compartments in demyelinating lesions, and that it can result in the generation of ectopic impulses.

Action Potentials↗

Connectivity of ectopic neurons in the molecular layer of the somatosensory cortex in autoimmune mice.

Approximately 50% of New Zealand Black mice (NZB/BINJ) and 80% of NXSM-D/EiJ mice prenatally develop neocortical layer I ectopias, mostly in somatosensory cortices. These cortical anomalies are similar to those seen in the brains of individuals with dyslexia. Neurofilament staining revealed a radial column of tightly packed fiber bundles in the layers underlying ectopias. This suggested that the connectivity of the ectopic neurons was aberrant. The present study used the tracers 1,1'-dioctadecyl- 3,3,3',3'-tetramethylindo- carbocyanine perchlorate (DiI) and biotinylated dextran amine (BDA) to more thoroughly explore the cortical and thalamic connectivity of the ectopias. DiI placement into ectopias again revealed a distinct bundle of fibers extending from the ectopic neurons to the deep cortical layers. This bundle split in the white matter with some fibers traveling to the corpus callosum and others to the internal capsule. Thalamic connections were concentrated in the ventrobasal com- plex (VB) and posterior thalamic nucleus group (Po). Injections of BDA into VB revealed reciprocal connections between VB and the ectopic cortical neurons. Ipsilateral corticocortical projections were seen between ectopias in primary somatosensory and motor and secondary somatosensory cortices, but no contralateral connections of the ectopic neurons were seen. These findings confirm the notion that layer I ectopias are anomalously connected by comparison to neurons in homologous cortex, which may underlie widespread dysfunction of brains containing ectopias.

Animals↗