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Biomedical subjects

I S Fraser

Publications and source records attributed to I S Fraser.

At least 19 recordsLinked to original sources
PubMed2002

Analysis of the Ki-67 antigen at the invasive tumour front of human oral squamous cell carcinoma.

BACKGROUND: It is hypothesised that cell proliferation, as measured by the Ki-67 labelling index (LI) at the invasive tumour front (ITF) was directly related to the histological grade in human oral squamous cell carcinomas (SCCs). METHODS: Tissues from 42 human oral SCCs were collected and stained with an antibody directed against the Ki-67 antigen using an advanced polymer staining system. Quantitation of the immunopositive cells was performed on two parallel sections at the invasive tumour front (ITF), using an image analyser. The Ki-67 LI was expressed as the number of positive nuclei/mm2 of epithelium. The control tissue used was normal epithelium at the excision margin. RESULTS: The mean Ki-67 LI for oral SCCs at the ITF was significantly greater than that for the excision margin tissue (P < 0.0001). There was a positive association between increasing Ki-67 LI and increasing Broders' grade (P < 0.05), with a well-differentiated tumour having the lowest mean Ki-67 LI (1549 +/- 806) and a poorly differentiated tumour having the highest value (2232 +/- 771). A similar trend was observed between the mean Ki-67 LI and Bryne's multifactorial grading system. CONCLUSIONS: It was concluded from this study that cell proliferation (as measured by the Ki-67 antigen) at the ITF had a strong positive relationship with histological grading in human oral SCC.

Analysis of Variance↗
PubMed2002

Surface vascularization and endometrial appearance in women with menorrhagia or using levonorgestrel contraceptive implants. Implications for the mechanisms of breakthrough bleeding.

BACKGROUND: Women using progestogen-only contraceptives are commonly troubled by irregular bleeding. Endometrial vessel breakdown and repair is thought to be locally regulated under the indirect influence of sex steroids. Most information about endometrial vessels is derived from blind biopsies taken in an outpatient setting. Hysteroscopy allows in-vivo observation of the whole endometrial surface, including vessel morphology, distribution and areas of bleeding, as well as information about non-vascular structures that may not be accessible from biopsies. METHODS: Hysteroscopies were performed on 34 women using the levonorgestrel contraceptive implant system (Norplant(TM)) and in a comparison group of 20 women complaining of menorrhagia due to ovulatory dysfunctional bleeding. The images were captured and vascular appearances assessed using image analysis. RESULTS: The percentage of the superficial endometrium covered with blood vessels was found to be significantly greater in Norplant users compared with the comparison group (P = 0.0006). More superficial vessels were seen in those with recent frequent or prolonged bleeding and spotting (P < 0.0001). In Norplant users, but not in the comparison group, superficial vascular distribution was predominantly patchy (P < 0.0001). Unusual vascular appearances classified as 'neovascular' (P < 0.0001) and 'mosaic' (P < 0.0001) patterns were commonly seen in Norplant users but not in the comparison group. The hysteroscopic appearance of the endometrial epithelium, glands and stroma also differed between Norplant users and women with menorrhagia. Apparent shedding of the superficial endometrium was commonly seen by hysteroscopy in Norplant users during a bleeding episode (P < 0.0001). Prominent gland openings with thick mucus were commonly seen in Norplant users and small sessile polyps were seen in six cases. CONCLUSIONS: These hysteroscopic observations provide further evidence that exposure to progestogens alters the superficial endometrial vasculature and may interfere with angiogenesis.

Adult↗
PubMed2001

Endometrial bleeding in hormone replacement therapy users: preliminary findings regarding the role of matrix metalloproteinase 9 (MMP-9) and tissue inhibitors of MMPs.

OBJECTIVE: To establish the effect of hormone replacement therapy (HRT) on the expression of matrix metalloproteinase 9 (MMP-9) and the tissue inhibitor of MMPs, TIMP-1, in the endometrium of postmenopausal and perimenopausal women. DESIGN: Prospective observational study. SETTING: United Kingdom teaching hospital. PATIENT(S): Thirty-one perimenopausal and postmenopausal HRT recipients, with a control group of eight postmenopausal women not undergoing HRT. INTERVENTION(S): Prospective record of bleeding patterns and endometrial biopsy. MAIN OUTCOME MEASURE(S): Endometrial histology, bleeding patterns, MMP-9, and TIMP-1 expression. RESULT(S): MMP-9 and TIMP-1 are expressed in benign postmenopausal endometrium. Expression of both molecules is reduced in HRT recipients compared with non-HRT recipients. CONCLUSION(S): Exposure to HRT appears to alter endometrial expression of MMP-9 and TIMP-1 and also the local balance between these molecules. This alteration may promote breakdown of the endometrial extracellular matrix and blood vessels and hence bleeding.

Base Sequence↗
PubMed2001

Estimating menstrual blood loss in women with normal and excessive menstrual fluid volume.

OBJECTIVE: To examine the relationship between total fluid volume at menstruation and the volume of blood loss, and to assess the feasibility of using total fluid volume to estimate menstrual blood loss. METHODS: Fifty-three women were studied over two menstrual periods each. Hemoglobin in menstrual pads and tampons was measured using the alkaline hematin technique; total menstrual fluid volume was simultaneously measured using a weighing technique and meticulous care to avoid evaporation. RESULTS: Despite period-to-period change in measured total menstrual fluid and menstrual blood loss volumes, there was a significant correlation between total fluid volume and blood loss (r =.93, P <.001). Blood comprised 48% of total menstrual flow for women with moderately heavy blood loss (>60 mL) and 50% for women with excessive blood loss (>100 mL). Regression estimation of blood loss from total fluid volume was reasonably accurate. For clinical purposes, estimated blood volumes correctly classified 98% of periods in terms of actual blood loss as normal (<60 mL blood), moderately heavy (60-100 mL), or excessive (>100 mL). CONCLUSION: If total fluid volume is measured carefully, the estimate of actual blood loss is sufficiently accurate for clinical purposes. This simple technique has considerable clinical potential, and inexpensive commercial packs for this purpose could easily be developed.

Blood Volume↗
PubMed2001

Computer-generated, three-dimensional reconstruction of histological parallel serial sections displaying microvascular and glandular structures in human endometrium.

This paper describes a technique to develop high-resolution three-dimensional (3D) images of microvasculature structures in curettage, hysterectomy or endometrial resection biopsies using parallel histological serial sections. Employing a labelled streptavidin-biotin-alkaline phosphatase (LSAB(+)) method and visualising by using DAB(+) with the primary antibody, mouse anti human Q-Bend-10, the images were directly digitised from a light microscope into the KS400 Universal Image Processing and Analysis software via a CCD colour camera; binary images of the structures were created and the binary images were exported into VoxBlast 3D rendering software to view still and rotating 3D images on a computer monitor. This in turn enabled hard copies of the full sequence to be printed.

Endometrium↗
PubMed2001

The promise and performance of progestogens as contraceptives.

Progestogens were first suggested as possible contraceptives in the 1920s, but it was not until the early 1960s that effective progestogen-only contraceptive methods were developed. Since then it has become possible to deliver a range of different progestogens at varying doses, by a variety of routes, over greatly differing durations of time. Some of these systems have demonstrated extraordinarily high contraceptive efficacy with relatively few side-effects apart from unpredictable, but almost universal, disturbances of the menstrual pattern. It is now recognized that some systems may exhibit substantial non-contraceptive health benefits, which should become an important part of the overall performance profile of each method. The high technology and differing attributes associated with some of the systems raise important considerations in relation to user's perceptions and programmatic requirements. Overall, progestogens are able to offer women a varied range of valuable choices for contraception. The differing performance characteristics of these methods now provide women with a major portion of their current contraceptive choices.

Animals↗
PubMed2001

A randomised controlled trial comparing a dilating vaginal speculum with a conventional bivalve speculum.

Cervical smears are traditionally taken with the aid of a metal or disposable plastic bivalve speculum. Many women complain of discomfort with these specula. This study compares the efficacy and women's experiences of a new 'dilating speculum' called the Veda-scope, with a conventional metal bivalve speculum (Pederson). The aims of this study were: to determine whether the Veda-scope provides adequate visualisation of the cervix and vaginal walls and an adequate cervical cytology specimen; and to compare user acceptability and women's levels of comfort between the Veda-scope and the bivalve speculum. Sixty-four women were randomised to be examined with the Veda-scope and 60 with the bivalve speculum, by one of two operators. Each woman completed a questionnaire that included subjective views of their previous cervical smear experiences, and acceptability of the examination at the study consultation. Cytologists were blinded as to which speculum was used for cervical sampling. Of women examined, 7-83% of women found Veda-scope examinations comfortable, compared to 38-62% of women who found examinations with the bivalve comfortable; 94% of the women preferred the 'comfort' of the Veda-scope. The Veda-scope was as good as the bivalve speculum in providing samples for cytological analysis following the initial learning curve, and also provided markedly superior magnified views of the cervix and vaginal fornices.

Adult↗
PubMed2000

Forty years of combined oral contraception: the evolution of a revolution.

The combined oral contraceptive (COC) pill has become an integral part of fertility choice in almost every country since its introduction in 1960 in the United States. It was the first contraceptive method to provide sexual freedom of choice for women through reliable personal, private control of fertility. Modern, very low-dose pills have maintained a high degree of contraceptive efficacy, but the margin for error in pill-taking appears much smaller. These COCs have a much lower incidence of side effects and serious complications than early high-dose COCs. Serious health risks from venous thromboembolism are rare, and not measurably higher for pills containing third-generation compared with earlier progestogens. Most women feel very well taking modern COCs, but myths about these drugs still abound. Most non-contraceptive health benefits of COCs are still not widely appreciated in spite of much evidence. Controversy still persists over the association between COC use and breast cancer. Although slightly more breast cancers are detected in current COC users (relative risk 1.24; 95% CI, 1.15-1.33), they are less advanced and less aggressive. Some women have pre-existing medical risk factors for COC use, and a detailed history for cardiovascular risk factors is one of the most important precautions.

Contraceptives, Oral, Combined↗
PubMed2000

Progestogens versus oestrogens and progestogens for irregular uterine bleeding associated with anovulation.

BACKGROUND: Dysfunctional uterine bleeding (DUB) is "excessively heavy, prolonged or frequent bleeding of uterine origin which is not due to pregnancy or to recognizable pelvic or systemic disease". Anovulation may be inferred from a number of observations but in the normal clinical situation, anovulation is often assumed when a woman presents with heavy, prolonged or frequent bleeding, particularly in those at the extremes of reproductive life and in women known to have the polycystic ovarian syndrome. Menstrual bleeding that is irregular or excessive is usually poorly tolerated by the majority of women. Changes in the length of the menstrual cycle generally imply disturbances of the hypothalamo-pituitary-ovarian (HPO) axis. In anovulatory DUB with acyclic (irregular) oestrogen production there will be no progesterone withdrawal from oestrogen primed endometrium and so cycles are irregular. Prolonged oestrogen stimulation may cause a build up of endometrium with erratic bleeding as it breaks down and is expelled. This is the rationale for using cyclical progestogens during the second half of the menstrual cycle in order to provoke a regular withdrawal bleed. Continuous progestogen is intended to induce endometrial atrophy and hence to prevent oestrogen-stimulated endometrial proliferation. Progestogens, and oestrogens and progestogens in combination are already widely used in the management of irregular or excessive bleeding due to DUB, but the regime, dose and type of progestogen used varies widely with little consensus about the optimum treatment approach. OBJECTIVES: To determine the effectiveness and acceptability of progestogens alone, and oestrogens and progestogens in combination in the management of irregular bleeding associated with anovulation. SEARCH STRATEGY: The search strategy of the Menstrual Disorders Group was used to identify all randomised trials of progestogens alone or in combination with oestrogens in the management of irregular menstrual bleeding associated with anovulation. In addition a search of the Cochrane Controlled Trials Register was undertaken. SELECTION CRITERIA: All randomised controlled trials of progestogens (via any route) alone or in combination with oestrogens in the treatment of irregular bleeding associated with anovulation. DATA COLLECTION AND ANALYSIS: Study quality assessment and data extraction were carried out independently by two reviewers. Both reviewers were experts in the content matter. MAIN RESULTS: No randomised trials were identified which compared progestogens with oestrogens and progestogens in the management of irregular bleeding associated with anovulation. Only one small, non-randomised study compared two progestogen regimes in the management of heavy and irregular bleeding in subjects with confirmed anovulation. One randomised study compared the effects of two progestogens on endometrial histology in subjects with a variety of menstrual symptoms, half of whom had cystic glandular hyperplasia. No studies were found which compared progestogens with oestrogens and progestogens in combination or with placebo in the management of irregular bleeding associated with anovulation. REVIEWER'S CONCLUSIONS: There is a paucity of randomised studies relating to the use of progestogens and of oestrogens and progestogens in combination in the treatment of irregular bleeding associated with anovulation. Further research is needed to establish the role of these treatments in the management of this common gynaecological problem.

Adult↗
PubMed2000

Vaginal epithelial surface appearances in women using vaginal rings for contraception.

Vaginal inspections using colposcopy before insertion of contraceptive vaginal rings and at 2-month intervals during ring use were conducted on 169 users of four different formulations. The rings studied released Nestorone alone (50, 75, 100 g daily over 6 months); ethinyl estradiol: Nestorone (30:100 and 15:150 g daily over 6 months); ethinylestradiol:norethindrone acetate (20:1000 and 15:1000 g daily over 4 months); and ethinyl estradiol:norethindrone acetate (20:1000 g daily over 12 months). A total of 88 altered or atypical conditions of the vaginal surface appearance were recorded in 507 inspections (17.4% of inspections). Many of these atypical appearances were quite subtle. The incidence was significantly higher (p <0.01) than in the single pretreatment examinations (11 in 158 inspections; 7.0%), but closely matched that of a "control group" of sexually active women who were the subject of an earlier study by the same investigators. In that study, the incidence was 18% (57 atypical conditions in 317 inspections). In all, 83% of atypical conditions identified in the vagina during ring use had disappeared by the next scheduled colposcopy despite continued ring use. Findings of potential significance were conservatively defined as all ulcerations, those abrasions and ecchymoses that were >0.5 cm in any direction, and fields of five or more petechiae. Findings fitting those criteria comprised 30% of atypical conditions in ring users, 33% in the control group, and 27% pretreatment. The corresponding incidence as a percentage of inspections were 5.3%, 6. 0%, and 2.5% in the ring users, control groups, and pretreatment groups, respectively. These differences were not statistically significant. The findings suggest that the vaginal rings included in the studies contributed little, if at all, to clinically significant lesions or to total lesion incidence. Further definition would require a larger and longer-term study with matched controls.

Adolescent↗
PubMed2000

A detailed analysis of menstrual blood loss in women using Norplant and Nestorone progestogen-only contraceptive implants or vaginal rings.

Changes to the pattern of menstrual bleeding are almost universal in women using progestogen-only methods of contraception, and are an important cause of discontinuation of these methods. The present study was designed to explore the changes in menstrual bleeding patterns and objectively measure menstrual blood loss (MBL) in 110 women before and during one year of use of 4 different progestogen-only contraceptives: Norplant subdermal levonorgestrel implants; Nestorone progestogen 4-cm or 6-cm implants nominally delivering 100 microg or 150 microg daily; or a vaginal ring (CVR) delivering 100 microg of Nestorone (NES) daily (CVR users were limited to only 6 months of use). Groups could not be directly compared because of the differences in numbers of subjects and durations of treatment. The total MBL during each of the three 8-week collection periods during treatment decreased significantly in each group compared to the total blood loss in the two control cycles (greater than 50% decrease in all groups during the first 6 months), although the differences between individual women at the extremes remained considerable. The highest blood loss measured on any single day during the treatment collection periods was significantly reduced (p <0.001) in users of all four devices in all three collection periods compared to the control period (CVR users did not have a 3rd collection period). The Nestorone-releasing CVR was associated with an 88% reduction in mean MBL and a high incidence of amenorrhea at 6 months. There was considerable variation in percentage reduction in total blood loss at 6 and 12 months between individual women ranging from 100% (women with amenorrhea) to a small minority experiencing an increase compared with control cycles. The increases in measured blood loss during treatment were almost entirely in women with light bleeding in the control period and were related to prolonged episodes of light bleeding rather than heavy bleeding. Women contemplating use of a progestogen-only contraceptive method need to be counseled about alterations to the menstrual cycle but can be reassured that total blood loss will usually be much less than with normal cycles.

Administration, Intravaginal↗
PubMed2000

A randomized comparison of the effects on vaginal and cervical epithelium of a placebo vaginal ring with non-use of a ring.

Little is known about the effects of contraceptive vaginal rings on the vaginal surface epithelium, although most studies have not demonstrated any significant deleterious effect. However, one study found that some medium-to-long-term levonorgestrel-releasing ring users developed chronic erythematous and ulcerative lesions in the posterior vaginal fornix. Subsequently, this ring was completely redesigned (IVR-2) with different dimensions and much greater flexibility. The first version of IVR-2 was designed as a placebo ring to explore effects on the vagina and cervix without addition of a progestogen. One-hundred-sixty-six healthy sexually active women volunteers were recruited in four centers and randomly assigned for 6 months to either placebo ring use or control (non-use) using a predetermined randomization code generated by WHO in a 2:1 ratio. Careful inspections of the vaginal and cervical epithelium were performed with a colposcope at admission and at 2-month intervals. No clinically significant lesions were detected in any center either among ring users or controls. However, a number of minor changes in appearance of the vaginal and cervical epithelium (erythema, petechiae, ecchymosis, and minor aceto-white changes) were described from the Sydney Center, some of which were present on admission and some of which were found on subsequent examination. Ten of eleven "red" changes on the cervix and vagina were noted in IVR-2 users, and only one in the controls, suggesting a contribution by the IVR-2 to minor epithelial surface changes. Five of ten resolved completely with continued ring use. There was no correlation in this study between epithelial changes and cigarette smoking or frequency of intercourse in the 14 days prior to colposcopic examination but a significant relationship between tampon use in the last 7 days and all epithelial changes (p = 0.05) and especially red changes (p = 0. 027) was noted. Red changes were significantly less likely to be found among condom users (p = 0.007). The IVR-2 placebo ring did not produce clinically significant changes in the vaginal epithelium and cervical mucosa and a carefully controlled and randomized study should be considered to compare the epithelial appearances in women using a placebo IVR-2 and one releasing 20 microg levonorgestrel.

Biopsy↗
PubMed2000

Menstrual blood loss measured 5-6 years after endometrial ablation.

OBJECTIVE: To examine objectively the long-term efficacy of endometrial ablation for menorrhagia. METHODS: Thirty-nine women with menorrhagia due to ovulatory dysfunctional bleeding treated previously by rollerball ablation were followed up 5-6 years later. Menstrual blood in sanitary towels was measured with the alkaline hematin technique in 26 women who were still premenopausal and in whom menstrual blood loss had been measured before and immediately after the original ablation. RESULTS: Mean (+/- standard deviation [SD]) menstrual blood loss (per menstrual period) was reduced from 90 mL +/- 14.4 before ablation to 3.8 mL +/- 2.1 at 3 months, 1.8 mL +/- 1.0 at 6 months, and 3.3 mL +/- 1.3 at 5-6 years after ablation. In women who were still menstruating, the mean hemoglobin concentration rose significantly from 126 to 135 g/L (P = .022). CONCLUSION: Rollerball endometrial ablation is a highly effective long-term therapy for carefully selected women with menorrhagia due to ovulatory dysfunctional uterine bleeding.

Adult↗
PubMed2000

Culturing endothelial cells of microvascular origin.

There is considerable divergence of opinion on the best methods for the isolation and in vitro culture of microvascular endothelium. Reports have either only described the isolation without mentioning culture conditions or have not fully defined the cell population being cultured. Even at the close of the 20th Century, the isolation and in vitro culture of endothelial cells of microvasculature origin still proves to be technically difficult and many questions remain. These questions need to be addressed by improvements to current methods of isolation and culture of Endothelial cells. A number of more 'high-tech' approaches to this isolation are being explored currently. Use of a more definitive panel of antibodies for immunocytochemical characterization, should enable a more confident characterization of the endothelial cell preparations cultured in vitro. Cell adhesion molecules such as ELAM and VCAM can be used to assist in determining cell population purity.

Capillaries↗
PubMed2000

Clinical implications of disturbances of uterine vascular morphology and function.

Menstrual disturbances are one of the most common problems presenting to the gynaecologist. In order for the endometrium to bleed, vessels must break down. Disruption in the regulation of endometrial vascular growth and function has been found in association with spontaneous and sex steroid-induced disturbances of menstrual bleeding. Although circulating oestrogens and progestogens influence the endometrial vessels, this effect appears to be indirect, and regulation is primarily via local factors. Deficient vasoconstriction and haemostasis with excessive fibrinolysis is seen in menorrhagia. Breakthrough bleeding in users of progestogen-only contraceptives is associated with increased superficial vascular fragility and disruptions in the supporting basement membrane. Blood vessels in uterine fibroids are abnormal in distribution and appearance. Adenomyosis is also commonly associated with menstrual disturbance, and alterations in vascular distribution suggest altered angiogenesis. Successful human embryo implantation requires endometrial vascular breakdown. Excessive thrombosis associated with the antiphospholipid syndrome may interfere with this re-modelling and compromise implantation. Arteriovenous malformations are a rare but important cause of excessive or irregular vaginal bleeding. Abundant vessels with abnormal morphology, associated with aberrant angiogenesis can be seen, and embolization of these vessels may be an effective conservative treatment. Improved understanding of the regulation of the uterine vasculature is likely to lead to targeted therapies to prevent unscheduled vascular breakdown and to control menstrual disturbance at an endometrial level.

Arteriovenous Malformations↗
PubMed2000

The measurement of endometrial perfusion in norplant users: a pilot study.

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.

Adult↗