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Ian S Fraser - One of the best experts on this subject based on the ideXlab platform.
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a functional model for progestogen induced breakthrough bleeding
Human Reproduction, 2000Co-Authors: M Hickey, Ian S FraserAbstract:During the past 5 years, a number of important advances have been made in our understanding of the mechanisms of sex steroid-induced breakthrough bleeding (BTB). These observations suggest that superficial endometrial Vascular Fragility may be the mechanism underlying BTB, and molecular changes in the microvasculature as well as hysteroscopic observations have supported this hypothesis. This paper aims to present a unified picture of our current understanding of BTB, particularly that associated with progestogens, to indicate current gaps in our knowledge and possible directions for future research.
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superficial endometrial Vascular Fragility in norplant users and in women with ovulatory dysfunctional uterine bleeding
Human Reproduction, 2000Co-Authors: Martha Hickey, D M Dwarte, Ian S FraserAbstract:The aim of this study was to develop an objective test for superficial endometrial Vascular Fragility at hysteroscopy and to apply this test to women using Norplant® for contraception and to women with ovulatory dysfunctional uterine bleeding (DUB). A prospective observational study was carried out in 34 Norplant users and 20 women with menorrhagia due to ovulatory DUB. Superficial endometrial Vascular Fragility was assessed at hysteroscopy by observing the source and extent of frank and subepithelial bleeding during controlled collapse and redistension of the uterine cavity. Superficial endometrial blood vessels were more fragile in Norplant users compared to women with DUB (?(2) = 11.60 P = 0.02). Superficial endometrial petechine (?(2) = 37.9 P < 0.0001) and ecchymoses (?(2) = 42.2 P = 0.0001) were more frequently observed in the Norplant users than in the menorrhagia group. In Norplant users superficial endometrial Vascular Fragility was increased in those with frequent bleeding or spotting during the past 30 days (?(2) = 6.15 P = 0.01) and in those who were examined during a bleeding episode (?(2) = 5.3 P = 0.02). Fragility was increased in the menorrhagia group during the perimenstrual period (days 24 to 05; ?(2) = 12.83 P = 0.01). There was no obvious relationship between subepithelial bleeding and circulating concentrations of oestradiol and progesterone. (authors)
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the measurement of endometrial perfusion in norplant users a pilot study
Human Reproduction, 2000Co-Authors: Martha Hickey, Colin Carati, Frank Manconi, B J Gannon, D M Dwarte, Ian S FraserAbstract:The use of progestogens without oestrogen is commonly associated with irregular menstrual bleeding. Oestrogens and progestogens are both thought to influence endometrial perfusion; changes in endometrial perfusion may contribute to Vascular Fragility and breakdown. In this study, endometrial perfusion was measured using laser-Doppler fluxmetry in women in the secretory phase of the menstrual cycle before and 4-6 weeks after insertion of the low-dose long-acting levonorgestrel contraceptive implant system, Norplant. Endometrial perfusion was also measured in women exposed to Norplant for up to 19 months. There was no significant difference between endometrial perfusion in control cycles (27.2 flux units +/- 5.5, SEM) and at 4-6 weeks after Norplant insertion (16.3 flux units +/- 5.0), a time when irregular bleeding and spotting are common. Endometrial perfusion was no different from controls after longer periods of Norplant exposure (35.7 flux units +/- 7.2). No direct relationships between endometrial perfusion and plasma concentrations of ovarian steroid hormones were demonstrated. Short-term endometrial vasomotion was largely abolished during Norplant exposure.
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changes in Vascular basement membrane in the endometrium of norplant users
Human Reproduction, 1999Co-Authors: Martha Hickey, Frank Manconi, Masoumeh Simbar, R Markham, Lawrence Young, Pamela J Russell, Ian S FraserAbstract:Progestogen-only contraception is almost invariably associated with changes in menstrual bleeding patterns. Changes in the endometrial vasculature and in particular an increase in Vascular Fragility may contribute to this bleeding. In this study endometrial Vascular density and endothelial cell basement membrane components were examined using immunohistochemistry before and after insertion of Norplant. Endometrial Vascular density was increased from a mean (+or- SEM) of 189.6 +or- 7.0 vessels/sq. mm during the control cycle to 253.9 +or- 80.7 vessels/sq. mm at 2-13 weeks of Norplant exposure and to 212.7 +or- 12.9 vessels/sq. mm at 14-42 weeks. During the control cycle a mean of 161.4 +or- 4.5 vessels/sq. mm stained for collagen IV (85% of all vessels) while at 2-13 weeks 144.5 +or- 13.0 vessels/sq. mm stained for collagen IV (57% of all vessels) (t ratio = 2.08 P = 0.0057). By 14-42 weeks 71% of vessels (151.0 +or- 9.8) vessels/sq. mm were surrounded by collagen IV. This was not significantly different from control values (t ratio = 2.03). Endometrial Vascular laminin was also reduced following Norplant insertion from a mean of 176.0 +or- 4.2 vessels/sq. mm in the control cycle (93% of vessels) to 156.3 +or- 6.7 vessels/sq. mm at 2-13 weeks of exposure (57% of vessels) (t ratio = 2.08 P = 0.01). By 14-42 weeks of exposure to Norplant 162.5 +or- 9 vessels/sq. mm (76%) stained for laminin. This was not significantly different from control values (t ratio = 2.04). Endometrial Vascular heparan sulphate proteoglycan (HSPG) was reduced from 58.6 +or- 3.0 vessels/sq. mm during the control cycle (31% of vessels) to 43.6 +or- 5.6 vessels/sq. mm (only 17% of vessels) at 2-13 (t ratio = 2.08 P =0.025). At 14-42 weeks only 19% of vessels stained for HSPG (41.3 +or- vessels/sq. mm; t ratio = 2.04 P = 0.009). (authors)
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endometrial vasculature in norplant users preliminary results from a hysteroscopic study
Human Reproduction, 1996Co-Authors: Martha Hickey, Ian S Fraser, D M Dwarte, Sian GrahamAbstract:Long-acting progestogenic contraceptives are frequently associated with disturbances of menstrual bleeding patterns. In particular, irregular, frequent and prolonged bleeding are commonly seen. The mechanism of this irregular bleeding is unknown, but changes in the endometrial vasculature are thought to be of importance. In endometrial biopsies from Norplant users, an increase in endometrial microVascular density has been observed after 3-12 months. Morphological changes in endometrial capillaries following progestogen exposure have suggested an increase in Vascular Fragility. Little is known about the structure and function of the endometrial vasculature in vivo following exposure to exogenous contraceptive steroids. This study has developed techniques for the assessment of Vascular Fragility by imposing a mechanical stress on the endometrium and observing subsequent bleeding under direct vision. The techniques were used in a preliminary examination between 1 and 9 months after Norplant insertion, and the study identified a number of morphological and functional characteristics of Norplant-exposed endometrium.
Martha Hickey - One of the best experts on this subject based on the ideXlab platform.
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superficial endometrial Vascular Fragility in norplant users and in women with ovulatory dysfunctional uterine bleeding
Human Reproduction, 2000Co-Authors: Martha Hickey, D M Dwarte, Ian S FraserAbstract:The aim of this study was to develop an objective test for superficial endometrial Vascular Fragility at hysteroscopy and to apply this test to women using Norplant® for contraception and to women with ovulatory dysfunctional uterine bleeding (DUB). A prospective observational study was carried out in 34 Norplant users and 20 women with menorrhagia due to ovulatory DUB. Superficial endometrial Vascular Fragility was assessed at hysteroscopy by observing the source and extent of frank and subepithelial bleeding during controlled collapse and redistension of the uterine cavity. Superficial endometrial blood vessels were more fragile in Norplant users compared to women with DUB (?(2) = 11.60 P = 0.02). Superficial endometrial petechine (?(2) = 37.9 P < 0.0001) and ecchymoses (?(2) = 42.2 P = 0.0001) were more frequently observed in the Norplant users than in the menorrhagia group. In Norplant users superficial endometrial Vascular Fragility was increased in those with frequent bleeding or spotting during the past 30 days (?(2) = 6.15 P = 0.01) and in those who were examined during a bleeding episode (?(2) = 5.3 P = 0.02). Fragility was increased in the menorrhagia group during the perimenstrual period (days 24 to 05; ?(2) = 12.83 P = 0.01). There was no obvious relationship between subepithelial bleeding and circulating concentrations of oestradiol and progesterone. (authors)
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the measurement of endometrial perfusion in norplant users a pilot study
Human Reproduction, 2000Co-Authors: Martha Hickey, Colin Carati, Frank Manconi, B J Gannon, D M Dwarte, Ian S FraserAbstract:The use of progestogens without oestrogen is commonly associated with irregular menstrual bleeding. Oestrogens and progestogens are both thought to influence endometrial perfusion; changes in endometrial perfusion may contribute to Vascular Fragility and breakdown. In this study, endometrial perfusion was measured using laser-Doppler fluxmetry in women in the secretory phase of the menstrual cycle before and 4-6 weeks after insertion of the low-dose long-acting levonorgestrel contraceptive implant system, Norplant. Endometrial perfusion was also measured in women exposed to Norplant for up to 19 months. There was no significant difference between endometrial perfusion in control cycles (27.2 flux units +/- 5.5, SEM) and at 4-6 weeks after Norplant insertion (16.3 flux units +/- 5.0), a time when irregular bleeding and spotting are common. Endometrial perfusion was no different from controls after longer periods of Norplant exposure (35.7 flux units +/- 7.2). No direct relationships between endometrial perfusion and plasma concentrations of ovarian steroid hormones were demonstrated. Short-term endometrial vasomotion was largely abolished during Norplant exposure.
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changes in Vascular basement membrane in the endometrium of norplant users
Human Reproduction, 1999Co-Authors: Martha Hickey, Frank Manconi, Masoumeh Simbar, R Markham, Lawrence Young, Pamela J Russell, Ian S FraserAbstract:Progestogen-only contraception is almost invariably associated with changes in menstrual bleeding patterns. Changes in the endometrial vasculature and in particular an increase in Vascular Fragility may contribute to this bleeding. In this study endometrial Vascular density and endothelial cell basement membrane components were examined using immunohistochemistry before and after insertion of Norplant. Endometrial Vascular density was increased from a mean (+or- SEM) of 189.6 +or- 7.0 vessels/sq. mm during the control cycle to 253.9 +or- 80.7 vessels/sq. mm at 2-13 weeks of Norplant exposure and to 212.7 +or- 12.9 vessels/sq. mm at 14-42 weeks. During the control cycle a mean of 161.4 +or- 4.5 vessels/sq. mm stained for collagen IV (85% of all vessels) while at 2-13 weeks 144.5 +or- 13.0 vessels/sq. mm stained for collagen IV (57% of all vessels) (t ratio = 2.08 P = 0.0057). By 14-42 weeks 71% of vessels (151.0 +or- 9.8) vessels/sq. mm were surrounded by collagen IV. This was not significantly different from control values (t ratio = 2.03). Endometrial Vascular laminin was also reduced following Norplant insertion from a mean of 176.0 +or- 4.2 vessels/sq. mm in the control cycle (93% of vessels) to 156.3 +or- 6.7 vessels/sq. mm at 2-13 weeks of exposure (57% of vessels) (t ratio = 2.08 P = 0.01). By 14-42 weeks of exposure to Norplant 162.5 +or- 9 vessels/sq. mm (76%) stained for laminin. This was not significantly different from control values (t ratio = 2.04). Endometrial Vascular heparan sulphate proteoglycan (HSPG) was reduced from 58.6 +or- 3.0 vessels/sq. mm during the control cycle (31% of vessels) to 43.6 +or- 5.6 vessels/sq. mm (only 17% of vessels) at 2-13 (t ratio = 2.08 P =0.025). At 14-42 weeks only 19% of vessels stained for HSPG (41.3 +or- vessels/sq. mm; t ratio = 2.04 P = 0.009). (authors)
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endometrial vasculature in norplant users preliminary results from a hysteroscopic study
Human Reproduction, 1996Co-Authors: Martha Hickey, Ian S Fraser, D M Dwarte, Sian GrahamAbstract:Long-acting progestogenic contraceptives are frequently associated with disturbances of menstrual bleeding patterns. In particular, irregular, frequent and prolonged bleeding are commonly seen. The mechanism of this irregular bleeding is unknown, but changes in the endometrial vasculature are thought to be of importance. In endometrial biopsies from Norplant users, an increase in endometrial microVascular density has been observed after 3-12 months. Morphological changes in endometrial capillaries following progestogen exposure have suggested an increase in Vascular Fragility. Little is known about the structure and function of the endometrial vasculature in vivo following exposure to exogenous contraceptive steroids. This study has developed techniques for the assessment of Vascular Fragility by imposing a mechanical stress on the endometrium and observing subsequent bleeding under direct vision. The techniques were used in a preliminary examination between 1 and 9 months after Norplant insertion, and the study identified a number of morphological and functional characteristics of Norplant-exposed endometrium.
M Osborne-pellegrin - One of the best experts on this subject based on the ideXlab platform.
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Rupture of the internal elastic lamina and Vascular Fragility in stroke-prone spontaneously hypertensive rats.
Stroke, 1991Co-Authors: M Coutard, M Osborne-pellegrinAbstract:We studied a possible relation between stroke and an enhanced susceptibility to rupture of the arterial internal elastic lamina by comparing stroke-prone spontaneously hypertensive rats with spontaneously hypertensive rats, which have a very low incidence of stroke. We quantified interruptions in the internal elastic lamina in certain arteries and studied the effect of beta-aminopropionitrile, an inhibitor of cross-link formation in collagen and elastic fibers, on rupture of the internal elastic lamina and on mortality in these two substrains. To eliminate any influence of higher blood pressure in the stroke-prone rats on the parameters studied, we used antihypertensive treatment to obtain equivalent blood pressures in the two substrains. Results showed that stroke sensitivity was associated with an enhanced early spontaneous rupture of the internal elastic lamina in the caudal artery, an increased susceptibility to beta-aminopropionitrile-induced rupture of the internal elastic lamina, and earlier mortality, mainly from aortic rupture, under beta-aminopropionitrile treatment. These findings suggest that stroke-prone rats have an enhanced minor connective tissue defect that is expressed by rupture of the internal elastic lamina and may be related, at least in part, to their greater Vascular Fragility and increased susceptibility to stroke.
Howard J. Jacob - One of the best experts on this subject based on the ideXlab platform.
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Identification of two susceptibility loci for Vascular Fragility in the Brown Norway rat
Physiological genomics, 2001Co-Authors: Eugenie L. Harris, Monika Stoll, Gregory T. Jones, Mary A. Granados, William K. Porteous, Andre M. Van Rij, Howard J. JacobAbstract:A trait of Vascular Fragility, characterized by the formation of abrupt defects within the elastic laminae of the abdominal aorta, has been identified in Brown Norway (BN) rats. These lesions are g...
D M Dwarte - One of the best experts on this subject based on the ideXlab platform.
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superficial endometrial Vascular Fragility in norplant users and in women with ovulatory dysfunctional uterine bleeding
Human Reproduction, 2000Co-Authors: Martha Hickey, D M Dwarte, Ian S FraserAbstract:The aim of this study was to develop an objective test for superficial endometrial Vascular Fragility at hysteroscopy and to apply this test to women using Norplant® for contraception and to women with ovulatory dysfunctional uterine bleeding (DUB). A prospective observational study was carried out in 34 Norplant users and 20 women with menorrhagia due to ovulatory DUB. Superficial endometrial Vascular Fragility was assessed at hysteroscopy by observing the source and extent of frank and subepithelial bleeding during controlled collapse and redistension of the uterine cavity. Superficial endometrial blood vessels were more fragile in Norplant users compared to women with DUB (?(2) = 11.60 P = 0.02). Superficial endometrial petechine (?(2) = 37.9 P < 0.0001) and ecchymoses (?(2) = 42.2 P = 0.0001) were more frequently observed in the Norplant users than in the menorrhagia group. In Norplant users superficial endometrial Vascular Fragility was increased in those with frequent bleeding or spotting during the past 30 days (?(2) = 6.15 P = 0.01) and in those who were examined during a bleeding episode (?(2) = 5.3 P = 0.02). Fragility was increased in the menorrhagia group during the perimenstrual period (days 24 to 05; ?(2) = 12.83 P = 0.01). There was no obvious relationship between subepithelial bleeding and circulating concentrations of oestradiol and progesterone. (authors)
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the measurement of endometrial perfusion in norplant users a pilot study
Human Reproduction, 2000Co-Authors: Martha Hickey, Colin Carati, Frank Manconi, B J Gannon, D M Dwarte, Ian S FraserAbstract:The use of progestogens without oestrogen is commonly associated with irregular menstrual bleeding. Oestrogens and progestogens are both thought to influence endometrial perfusion; changes in endometrial perfusion may contribute to Vascular Fragility and breakdown. In this study, endometrial perfusion was measured using laser-Doppler fluxmetry in women in the secretory phase of the menstrual cycle before and 4-6 weeks after insertion of the low-dose long-acting levonorgestrel contraceptive implant system, Norplant. Endometrial perfusion was also measured in women exposed to Norplant for up to 19 months. There was no significant difference between endometrial perfusion in control cycles (27.2 flux units +/- 5.5, SEM) and at 4-6 weeks after Norplant insertion (16.3 flux units +/- 5.0), a time when irregular bleeding and spotting are common. Endometrial perfusion was no different from controls after longer periods of Norplant exposure (35.7 flux units +/- 7.2). No direct relationships between endometrial perfusion and plasma concentrations of ovarian steroid hormones were demonstrated. Short-term endometrial vasomotion was largely abolished during Norplant exposure.
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endometrial vasculature in norplant users preliminary results from a hysteroscopic study
Human Reproduction, 1996Co-Authors: Martha Hickey, Ian S Fraser, D M Dwarte, Sian GrahamAbstract:Long-acting progestogenic contraceptives are frequently associated with disturbances of menstrual bleeding patterns. In particular, irregular, frequent and prolonged bleeding are commonly seen. The mechanism of this irregular bleeding is unknown, but changes in the endometrial vasculature are thought to be of importance. In endometrial biopsies from Norplant users, an increase in endometrial microVascular density has been observed after 3-12 months. Morphological changes in endometrial capillaries following progestogen exposure have suggested an increase in Vascular Fragility. Little is known about the structure and function of the endometrial vasculature in vivo following exposure to exogenous contraceptive steroids. This study has developed techniques for the assessment of Vascular Fragility by imposing a mechanical stress on the endometrium and observing subsequent bleeding under direct vision. The techniques were used in a preliminary examination between 1 and 9 months after Norplant insertion, and the study identified a number of morphological and functional characteristics of Norplant-exposed endometrium.
