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PubMed1997

Bcl-2 and Fas expression in eutopic and ectopic human endometrium during the menstrual cycle in relation to endometrial cell apoptosis.

OBJECTIVE: Our purpose was to investigate Bcl-2 and Fas expression in human eutopic and ectopic endometrium during the menstrual cycle in relation to endometrial cell apoptosis. STUDY DESIGN: Eutopic and ectopic endometrial samples were obtained from 29 patients with endometriosis, and eutopic endometrial tissue samples were obtained from 9 patients with uterine myoma. Bcl-2 and Fas expression were examined by immunohistochemical staining with specific monoclonal antibodies; Bcl-2 expression in eutopic endometrium was also examined by Western blotting and apoptotic cells were detected by the labeling of deoxyribonucleic acid fragments. RESULTS: In eutopic endometrium Bcl-2 was strongly expressed during the proliferative phase. Endometrial glandular cells showed evidence of cyclic changes in Bcl-2 expression, but cyclic changes were not apparent in peritoneal and ovarian endometriotic tissue. Fas expression was observed on glandular cells but not on stromal cells, and no cyclic changes in expression occurred in either ectopic or eutopic endometrium. Apoptotic cells were observed primarily in the glandular cells of the basal layer in eutopic endometrium during the late secretory and menstrual phases. CONCLUSION: The current study indicated that there was no apparent correlation between Bcl-2 or Fas expression with endometrial cell apoptosis. The absence of cyclic changes in Bcl-2 expression in ectopic endometrium implied a difference in the mechanisms of proliferation or differentiation between eutopic and ectopic endometrium.

Adult↗
PubMed2002

Osteopontin inhibits mineral deposition and promotes regression of ectopic calcification.

Ectopic calcification, the abnormal calcification of soft tissues, can have severe clinical consequences especially when localized to vital organs such as heart valves, arteries, and kidneys. Recent observations suggest that ectopic calcification, like bone biomineralization, is an actively regulated process. These observations have led a search for molecular determinants of ectopic calcification. A candidate molecule is osteopontin (OPN), a secreted phosphoprotein invariantly associated with both normal and pathological mineral deposits. In the present study, OPN was found to be a natural inhibitor of ectopic calcification in vivo. Glutaraldehyde-fixed aortic valve leaflets showed accelerated and fourfold to fivefold greater calcification after subcutaneous implantation into OPN-null mice compared to wild-type mice. In vitro and in vivo studies suggest that OPN not only inhibits mineral deposition but also actively promotes its dissolution by physically blocking hydroxyapatite crystal growth and inducing expression of carbonic anhydrase II in monocytic cells and promoting acidification of the extracellular milieu. These findings suggest a novel mechanism of OPN action and potential therapeutic approach to the treatment of ectopic calcification.

Animals↗
PubMed2001

Intraoperative radioguided thoracoscopic removal of ectopic parathyroid adenoma.

Twenty-five percent of primary hyperparathyroidism is caused by ectopic mediastinal parathyroid glands, with 2% of these not accessible to standard cervical surgical approaches. Advancement in video-assisted thoracoscopic surgical techniques has decreased the need for sternotomy to successfully remove these ectopic glands. The thoracoscopic approach, however, is limited by the surgeon's inability to always accurately visualize ectopic glands. Intraoperative radionuclide-guided dissection, using a thoracoscopic approach, provides a novel adjunct to the removal of occult ectopic parathyroid glands. We report a case of an occult ectopic parathyroid adenoma removed thoracoscopically using an intraoperative handheld gamma probe.

Adenoma↗
PubMed2003

Immunoexpression of hepatocyte growth factor and c-Met receptor in the eutopic endometrium predicts the activity of ectopic endometrium.

OBJECTIVE: To investigate the mitogenic and angiogenic activity of the eutopic and ectopic endometrium throughout the menstrual cycle and to examine whether the activity of the eutopic endometrium is useful to predict greater activity of the ectopic endometrium. DESIGN: Controlled clinicopathologic study using intact tissue. SETTING: Nagasaki University School of Medicine, Nagasaki, Japan. PATIENT(S): Fifteen infertile women with pelvic endometriosis and 10 women without endometriosis undergoing laparoscopy. INTERVENTION(S): Biopsies from the ectopic endometrium and the corresponding eutopic endometrium were collected. Immunohistochemical staining was performed using respective antibodies, and a computer analyzed modified quantitative-histogram (Q-H) score was used to quantify immunostaining. MAIN OUTCOME MEASURE(S): The immunoreactions of hepatocyte growth factor (HGF), its receptor, c-Met, vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA), and von Willebrand factor (VWF) in eutopic and ectopic endometrium were examined, and their relation with different revised American Society for Reproductive Medicine (r-ASRM) stages and the morphology of endometriosis was evaluated. RESULT(S): The immunoexpressions of HGF and c-Met were significantly higher in the eutopic endometrium of patients with endometriosis than in that of controls. The Q-H scores of HGF, c-Met, VEGF, PCNA, and microvessel density (MVD) were markedly higher in red peritoneal lesions when compared with other lesions. The Q-H scores did not reveal r-ASRM stage-dependent variation in any of these markers. We observed a significant correlation between the immunoexpressions of HGF, c-Met, and PCNA or microvessel counts. When we combined the Q-H scores of the glandular epithelium and stroma, we found that increased activity of the eutopic endometrium as measured by the immunoreaction of HGF, c-Met, VEGF, PCNA, and MVD was similar to highly active red lesions and was significantly higher than that of controls and other lesions. CONCLUSION(S): Immunoexpression of HGF and c-Met in the eutopic endometrium of patients with pelvic endometrioisis is possibly useful to predict greater activity of the ectopic endometrium.

Adult↗
PubMed1987

Serologic evidence of prior chlamydial infection in patients with tubal ectopic pregnancy and contralateral tubal disease.

Oviductal damage from infectious salpingitis is a principle cause of ectopic pregnancy. To examine the role of Chlamydia trachomatis in patients with ectopic pregnancy, 24 patients undergoing laparotomy for ectopic pregnancy were evaluated by assessment of chlamydial serology and chlamydial cultures of tubal biopsy specimens. The patients were divided into two groups based on the presence or absence of gross abnormalities in the fallopian tube contralateral to the ectopic gestation. Ten patients in group I showed gross evidence of chronic salpingitis in the contralateral tube; 14 patients in group II had normal-appearing contralateral tubes. Chlamydial cultures were negative in both groups. Chlamydial immunoglobulin M antibodies assayed by indirect microimmunofluorescence were negative in both groups (less than or equal to 1:32). Mean geometric immunoglobulin G titers for C. trachomatis were significantly higher in the patients with evidence of contralateral chronic salpingitis (78.9 versus 13.1). These findings suggest that C. trachomatis may be a major cause of oviductal damage, which predisposes to ectopic pregnancy.

Adult↗
PubMed1995

Plasminogen activators in ectopic and uterine endometrium.

OBJECTIVE: To investigate the expression of the plasminogen activator (PA)-plasmin system components in ectopic endometrium and in uterine endometrium from women with and without endometriosis. DESIGN: Plasminogen, PAs (urokinase and tissue plasminogen activator), and PA inhibitors (1 and 2) were detected by immunohistochemistry using a alkaline phosphatase staining method. RESULTS: No differences in staining were found between uterine endometrium of women with endometriosis and women without endometriosis with any of the antibodies used. However, we did find differences between uterine and ectopic endometrium. Although the expression of the components of the PA-plasmin system reflected the cyclic changes in the hormonal levels in uterine endometrium, ectopic endometrium maintained a very high level of plasminogen and urokinase in every sample. We were unable to detect the presence of PA inhibitors in either uterine or ectopic endometrium. CONCLUSIONS: There is no evidence that uterine endometrium from women with endometriosis is originally more able to implant than that of women without the disease because of an increase in their PA expression. The high levels of urokinase and plasminogen in ectopic endometrium may reflect a more invasive nature of the endometriotic implants in the peritoneal cavity.

Endometriosis↗
PubMed1996

Immunohistochemical characterization of stromal leukocytes in ovarian endometriosis: comparison of eutopic and ectopic endometrium with normal endometrium.

OBJECTIVE: To compare stromal leukocyte subpopulations in different phases of the menstrual cycle in eutopic and ectopic endometrium from women with ovarian endometriosis and in control endometrium. DESIGN: Retrospective immunohistochemical study. SETTING: Department of Pathology, Royal Victoria Infirmary, Newcastle-upon-Tyne, United Kingdom. PATIENTS: Paraffin-embedded tissue blocks from 30 patients with endometriosis and 30 control blocks from patients undergoing hysterectomy for nonendometrial pathology were retrieved from archive files. MAIN OUTCOME MEASURE: Quantitative assessment of defined stromal leukocyte subpopulations in eutopic, ectopic and control endometrium at different stages of the menstrual cycle. RESULTS: In the proliferative and early secretory phases, ectopic endometrium contained elevated numbers of CD45+, CD3+, and CD43+ cells but reduced percentages of CD68+ macrophages. The proportions of granulated cells were reduced in ectopic endometrium throughout the cycle. No differences were noted between eutopic endometrium from women with endometriosis and control endometrium. CONCLUSION: Differences between eutopic and ectopic leukocyte subpopulations with the exception of large granular lymphocytes may be due to the lack of cyclicity demonstrated by endometriotic lesions.

Endometriosis↗
PubMed1998

Bladder dysfunction: an integral part of the ectopic ureterocele complex.

PURPOSE: We evaluate whether bladder dysfunction is common in patients with ectopic ureterocele and, if so, whether it is an integral part of the ectopic ureterocele complex or a result of surgery. MATERIALS AND METHODS: From 1986 to 1995, 34 patients with a mean age of 10 months were treated for large or medium ectopic ureteroceles at our institution and 32 participated in postoperative followup. Bladder function was investigated by a careful history and repeat uroflowmetry, and residual urine estimation was assessed by ultrasound and cystometry. RESULTS: Of the 32 patients 19 had infrequent voiding and 3 had incontinence. Cystometric bladder capacity was increased to greater than 150% of the normal value for age in 15 of 27 patients (55%). Uroflowmetry revealed greater than 5 ml. residual urine in 15 patients (56%). Postoperatively no radiological signs of bladder neck obstruction were found. Increased bladder capacity and residual urine did not correlate with ureterocele size or location, or surgical procedure. There was no progression of bladder dysfunction with age. CONCLUSIONS: Children with ectopic ureterocele are at high risk for a high capacity bladder with incomplete emptying. This bladder dysfunction associated with ectopic ureterocele does not seem to be the result of surgery but an integral part of the disorder.

Female↗
PubMed1989

Ectopic vas deferens, imperforate anus and hypospadias: a new triad.

An ectopic vas deferens is a rare congenital anomaly frequently associated with rectal abnormalities. We describe 2 patients with ectopic vas deferens associated with an imperforate anus and hypospadias. There are 19 previous reports of patients with ectopic vas deferens, 5 of which were bilateral. One of our patients, a child with bilateral ectopic vas deferens, had the highest reported insertion of an ectopic vas deferens. The embryology and management of this rare condition are reviewed.

Anus, Imperforate↗
PubMed1997

A prospective analysis of the frequency, location, and curability of ectopic (nonpancreaticoduodenal, nonnodal) gastrinoma.

BACKGROUND: Extrapancreatic, extraduodenal and extralymphatic (ectopic) gastrinomas have been reported only rarely. The frequency, locations, and surgical outcome of these lesions are unknown. METHODS: From 1982 to 1997, 215 patients with Zollinger-Ellison syndrome were evaluated prospectively at the National Institutes of Health and 142 patients (66%) underwent standardized surgical exploration and resection. Eight patients (5.6%) (six men and two women; mean age, 41 years) had primary gastrinoma located in ectopic sites. Long-term follow-up was derived from a prospective database. RESULTS: Ectopic gastrinoma tissue was identified and resected in the liver (three patients), common bile duct (one patient), jejunum (one patient), omentum (one patient), pylorus (one patient), and ovary (one patient). Seven patients (88%) were cured biochemically after resection and five patients (63%) have sustained cures, with a mean follow-up of 7.5 years (range, 0.4 to 11.7 years). One patient with a jejunal primary gastrinoma had a biochemical recurrence at 2 years, and another with a primary hepatic gastrinoma had a recurrence 6 years after resection. A patient with a pyloric primary gastrinoma was not cured. CONCLUSIONS: Extraduodenal, extrapancreatic, and extranodal gastrinomas are encountered in 5.6% of patients who undergo exploration with curative intent. If no gastrinoma is found in the usual locations, other ectopic sites should be examined carefully. Resection of these primary ectopic tumors can lead to durable biochemical cures.

Adult↗
PubMed1999

Ectopic hidradenoma papilliferum: a case report and review of the literature.

Hidradenoma papilliferum is a benign, cystic, papillary tumor that occurs almost exclusively in women on the skin of the anogenital region. Nonanogenital (ectopic) hidradenoma papilliferum are rare. We describe a 72-year-old white man with an enlarging nodule in the region of the right triceps muscle; microscopic examination showed a hidradenoma papilliferum. The median age of patients with ectopic hidradenoma papilliferum is between 1 to 2 decades older than the average age range of lesion onset in patients with anogenital hidradenoma papilliferum. In contrast to anogenital hidradenoma papilliferum, nearly one half of the patients with ectopic hidradenoma papilliferum are men. Ectopic hidradenoma papilliferum occurs most frequently (60%) in the head and neck region. Eighty-five percent of cases are 1.5 cm in the greatest diameter or smaller. The race, clinical features, pathologic features, treatment, and prognosis for hidradenoma papilliferum occurring in anogenital and ectopic locations are similar.

Adenoma, Sweat Gland↗
PubMed2003

Ectopic synaptogenesis during retinal degeneration in the royal college of surgeons rat.

Rod photoreceptor-specific mutations cause ectopic synapses to form between cone photoreceptor terminals and rod bipolar cell dendrites in degenerating retinas of rhodopsin transgenic (P347L) pigs and retinal degeneration mice. Since the mutations occur in rod photoreceptor-specific genes in these two models, it is not known if ectopic synaptogenesis occurs specifically due to some rod photoreceptor cell-autonomous properties of a mutation or as a general consequence of photoreceptor degeneration. In the Royal College of Surgeons (RCS) rat, a mutation in the receptor tyrosine kinase gene, Mertk, causes failure of the retinal pigment epithelial (RPE) cells to phagocytose shed photoreceptor outer segments; subsequently, both rod and cone photoreceptors die. The non-phagocytic phenotype of the RCS rat is RPE cell-autonomous and the photoreceptors degenerate secondarily. Here we show that in 35-day-old RCS rats, where a majority of rod and cone photoreceptors remained, rod bipolar cell dendrites had abnormal (flat-contact type) synaptic contacts with rod and cone terminals. Demonstration of ectopic synapses in the RCS rat suggested that ectopic synaptogenesis could occur as a result of photoreceptor degeneration, even when the rods and cones were developmentally normal. This further supported the hypothesis that ectopic synaptogenesis may be a common step in the disease progression of different forms of retinal degeneration that include photoreceptor death as a feature, such as retinitis pigmentosa.

Animals↗
PubMed1986

Effect of encainide and flecainide on chronic ectopic atrial tachycardia.

In the treatment of chronic ectopic atrial tachycardia, standard antiarrhythmic therapy has been shown to be ineffective in the majority of patients. The intravenous and oral effects of two class IC antiarrhythmic drugs, encainide and flecainide, in five patients with chronic ectopic atrial tachycardia were studied using exercise testing, 24 hour long-term electrocardiography and programmed electrical stimulation. All patients had been treated unsuccessfully with at least four antiarrhythmic drugs. In two patients tachycardia was persistent, and in three patients tachycardia occurred intermittently for more than 12 hours/day. Intravenous encainide and flecainide at doses ranging from 0.3 to 2.0 mg/kg and from 0.5 to 1.5 mg/kg body weight, respectively, terminated atrial ectopic tachycardia in all patients. Oral encainide, 150 to 225 mg/day, completely suppressed ectopic atrial activity in four patients during a mean follow-up period of 8 +/- 3 months. In the remaining patient encainide markedly reduced the number of episodes of tachycardia. In three patients encainide had to be withdrawn because of intolerable side effects. These patients were well controlled with oral flecainide, 200 to 300 mg/day, without side effects. On the basis of these results, the efficacy of encainide and flecainide in the treatment of chronic ectopic atrial tachycardia appears to be not drug-specific but rather a general class IC property.

Adult↗
PubMed2000

Age and magnetic effects on ectopic bone formation induced by purified bone morphogenetic protein.

A mixture of heparin-Sepharose-purified bovine bone morphogenetic protein (BMP) and type I atellocollagen was implanted in the subcutaneous tissues of 4-week, 10-month and 18-month-old rats. The implants were removed at 7, 14 and 21 days after implantation. The effects of rat age on ectopic bone formation were evaluated on the explants using H&E staining, morphometric analysis, alkaline phosphatase (ALP) activity and calcium (Ca) content determination, as well as immunohistochemical staining of type IV collagen present in the basement membrane of blood vessels. On day 14 and 21, bone was observed in 4-week and 10-month-old rats but the amount of bone formed in the later was less than in the former. In 18-month-old rats, bone was first found focally in very limited regions of the explants on day 21 and the amount of bone was much less than in 4-week-old rats. At all periods ALP activity was higher in younger rats. On day 7, there were more blood vessels in the explants of 4-week-old rats than in those of 10- or 18-month-old rats. On day 14 and 21, more blood vessels were found in the central regions of the explants in 4-week-old rats than in the same regions in 10- or 18-month-old rats. The findings in the present study indicated that the rate and quantity of ectopic bone formation were reduced, and that the difference in blood vessel distribution might be related to the reduction in ectopic bone formation in aged rats, and suggest that the difference in blood vessel distribution is related to ectopic bone formation. Magnetism can stimulate ectopic bone formation induced by BMP.

Journal Article↗
PubMed2000

Delayed ectopic antler growth and formation of a double-head antler in the metacarpal region of a fallow buck (Dama dama L.) following transplantation of antlerogenic periosteum.

Autologous transplantation of antlerogenic periosteum to the metacarpal region of a fallow buck resulted in the formation of an ectopic pedicle within a few months after transplantation. In the following years the pedicle increased in size, but no ectopic antler development occurred. However, in the ninth year after transplantation a first antler of about 3 cm length grew from the ectopic pedicle. The hard ectopic first antler was not cast, and renewed antler growth, starting in late spring of the following year, led to the formation of a larger subsequent antler of 7.3 cm length. The latter exhibited a distal flattening (palmation) and a rudimentary basal coronet, thereby displaying morphological features typical of the subsequent antlers of fallow bucks. The results of the experiment indicate (1) that transformation from pedicle to antler growth can occur several years after pedicle initiation, when the pedicle has reached a certain threshold size, (2) that species and age specific features of antler morphology tend to be realized even in ectopic locations, and (3) that primary and subsequent antler growth was apparently triggered by cells of the pedicle periosteum, being derived from the transplanted antlerogenic periosteum. The findings thereby emphasize the importance of local factors in the control of pedicle/first antler transformation and antler morphogenesis.

Animals↗
PubMed1998

An analysis of risk factors associated with blood transfusion in ectopic pregnancy.

Objective: To determine the risk factors associated with blood transfusion in ectopic pregnancy.Methods: A retrospective chart review of the presentation and hospital course of ectopic pregnancies managed over 5 years at two hospitals was undertaken. Thirty-two variables, including demographics, presenting signs and symptoms, and intraoperative findings, were examined in univariate and multivariate logistic modeling.Results: Among 185 patients with histologically confirmed ectopic pregnancies who were managed surgically, 8.6% or 16 women required transfusion. Multivariate analysis of risk factors for blood transfusion demonstrated a statistically significant association with 1) initial hemoglobin <10 g/dL (odds ratio [OR] 38.8, 95% confidence interval [CI] 6.0-356.8) and 2) hCG levels >/= 6500 mIU (OR 18.1, 95% CI 3.6-158.1), as well as 3) abnormal bleeding on presentation (OR 0.08, 95% CI 0.007-0.42. Presence of two of these factors has a sensitivity of 82% (95% CI 48-98%) and a positive predictive value of 33% (95% CI 16-54%). No case had all three factors present.Conclusion: This report is, to our knowledge, the first regression analysis of risk factors for transfusion associated with ectopic pregnancy. It demonstrates that initial hemoglobin and hCG levels as well as abnormal bleeding on presentation are independent risk factors for blood transfusion in ectopic pregnancy.

Journal Article↗
PubMed1997

Assessment of an ectopic bone formation system with implantation of pelleted rat primary growth cartilage cells.

To assess the ectopic bone formation system, growth cartilage (GC) cells were implanted to ectopic sites, and the effect of the implanting sites and gender of animals on bone formation were examined. Each 5 x 10(5) batch of GC cells from young rat ribs was pelleted, cultured in calcification medium, and implanted to ectopic sites (in a peritoneal cavitiy or on subcutaneous muscle) in female or male rats. The implanted pellets formed bone after 3-4 weeks at the ectopic sites. Histological examination concluded that, first, a subcutaneous muscle site is more conductive to bone formation than a peritoneal cavity site and, second, the pelleted GC cells implanted in male rats formed bone more effectively than those in female rats. Therefore, at present, the ectopic bone formation system of pelleted primary GC cells onto subcutaneous muscle of male rats is an appropriate system for the evaluation of bone formation.

Animals↗
PubMed2004

Failure of fat cell proliferation, mitochondrial function and fat oxidation results in ectopic fat storage, insulin resistance and type II diabetes mellitus.

BACKGROUND: It is widely accepted that increasing adiposity is associated with insulin resistance and increased risk of type II diabetes. The predominant paradigm used to explain this link is the portal/visceral hypothesis. This hypothesis proposes that increased adiposity, particularly in the visceral depots, leads to increased free-fatty acid flux and inhibition of insulin-action via Randle's effect in insulin-sensitive tissues. OBJECTIVES: In this review, limitations of this paradigm will be discussed and two other paradigms that may explain established links between adiposity and insulin resistance/diabetes will be presented. (A) Ectopic fat storage syndrome. Three lines of evidence support this concept. Firstly, failure to develop adequate adipose tissue mass (also known as 'lipodystrophy') results in severe insulin resistance and diabetes. This is thought to be the result of ectopic storage of lipid into liver, skeletal muscle and the pancreatic insulin-secreting beta cell. Secondly, most obese patients also shunt lipid into the skeletal muscle, the liver and probably the beta cell. The importance of this finding is exemplified by several studies demonstrating that the degree of lipid infiltration into skeletal muscle and liver highly correlates with insulin resistance. Thirdly, increased fat cell size is highly associated with insulin resistance and the development of diabetes. Increased fat cell size may represent the failure of the adipose tissue mass to expand and therefore to accommodate an increased energy influx. Taken together, these observations support the 'acquired lipodystrophy' hypothesis as a link between adiposity and insulin resistance. Ectopic fat deposition is therefore the result of additive or synergistic effects including increased dietary intake, decreased fat oxidation and impaired adipogenesis. (B) Endocrine paradigm. This concept was developed in parallel with the 'ectopic fat storage syndrome' hypothesis. Adipose tissue secretes a variety of endocrine hormones such as leptin, interleukin-6, angiotensin II, adiponectin and resistin. From this viewpoint, adipose tissue plays a critical role as an endocrine gland, secreting numerous factors with potent effects on the metabolism of distant tissues. CONCLUSIONS: The novel paradigms of ectopic fat and fat cell as an endocrine organ probably will constitute a new framework for the study of the links between our obesigenic environment and the risk of developing diabetes.

Adipocytes↗