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Biomedical subjects

Ian S Fraser

Publications and source records attributed to Ian S Fraser.

18 recordsLinked to original sources
PubMed2007

Can we achieve international agreement on terminologies and definitions used to describe abnormalities of menstrual bleeding?

BACKGROUND: There is considerable worldwide confusion in the use of terminologies and definitions around the symptom of abnormal uterine bleeding (AUB), and these are leading increasingly to difficulties in setting up multinational clinical trials and in interpreting the results of studies undertaken in single centres. An international initiative was established to develop an agreement process to recommend clear, simple terminologies and definitions with the potential for wide acceptance. METHODS: After widespread consultation with relevant international and national organizations, journal editors and individuals, a modified Delphi process was developed to assess the current use of terminologies followed by a structured face-to-face meeting of 35 clinicians (mostly gynaecologists) and scientists in Washington. Focused small group discussions led to plenary assessment of concepts and recommendations using an electronic keypad voting system. RESULTS: There was almost universal agreement that poorly defined terms of classical origin used in differing ways in the English medical language should be discarded and that these should be replaced by simple, descriptive terms with clear definitions which have the potential to be understood by health professional and patient alike and which can be translated into most languages. The major recommendations were to replace terms such as menorrhagia, metrorrhagia, hypermenorrhoea and dysfunctional uterine bleeding. Suggestions for potentially suitable replacement terms and definitions are made. CONCLUSIONS: A simple terminology has been recommended for the description and definition of symptoms and signs of AUB. This manuscript should be a living document and should be part of an ongoing process with international medical and community debate. Classification of causes, investigations and cultural and quality of life issues should be part of the ongoing process.

Delphi Technique↗
PubMed2006

An ultrastructural study of microvascular inter-endothelial tight junctions in normal endometrium.

OBJECTIVE: To investigate changes in tight junctions between microvascular endothelial cells in normal endometrium. STUDY DESIGN: A quantitative transmission electron microscopy study of changes in the number of tight junctions per microvessel, and widths and lengths of individual junctions at different phases of the menstrual cycle. RESULTS: Two types of tight junctions were defined ("open" and "closed") which varied in the degree of separation between apposed plasma membranes of endometrial endothelial cells. Tight junction density was greater in proliferative than secretory phases (p<0.02). The width and length measurements of individual tight junctions changed during menstruation. CONCLUSIONS: The two types of tight junctional contacts and the changes in width and density may reflect variation in structure and function between adjacent endothelial cells. These junctions may have importance in the processes of implantation and menstruation.

Adolescent↗
PubMed2006

Nerve fibres in peritoneal endometriosis.

BACKGROUND: Endometriosis is a gynaecological disease that can be associated with severe pelvic pain; however, the mechanisms by which pain is generated remain unknown. METHODS: Peritoneal endometriotic lesions and normal peritoneum were prepared from women with and without endometriosis (n = 40 and 36, respectively). Specimens were also prepared from endosalpingiosis lesions (n = 9). These sections were stained immunohistochemically with antibodies against protein gene product 9.5, neurofilament (NF), nerve growth factor (NGF), NGF receptor p75 (NGFRp75), substance P (SP), calcitonin gene-related peptide (CGRP), acetylcholine (ACh) and tyrosine hydroxylase (TH) to demonstrate myelinated, unmyelinated, sensory, cholinergic and adrenergic nerve fibres. RESULTS: There were significantly more nerve fibres identified in peritoneal endometriotic lesions than in normal peritoneum (P < 0.001) or endosalpingiosis lesions (P < 0.001). These nerve fibres were SP, CGRP, ACh or TH immunoreactive. Many of these markers were co-localized. There was an intense NGF immunoreactivity near endometriotic glands, and NGFRp75 immunoreactive nerve fibres were present near endometriotic glands and blood vessels in the peritoneal endometriotic lesions. CONCLUSIONS: Peritoneal endometriotic lesions were innervated by sensory Adelta, sensory C, cholinergic and adrenergic nerve fibres. These nerve fibres may play an important role in the mechanisms of pain generation in this condition.

Adolescent↗
PubMed2006

Delivery systems for hormone replacement therapy.

The steroid hormones used for hormone replacement therapy in the menopausal transition and postmenopause can be administered by several different routes using a variety of delivery systems. The conventional approach to administration has been oral, and this is still the standard against which other routes are compared. However, there is a steadily increasing research development and popularity for alternative systems. Such systems can be geared to ultra low-dose delivery for local vaginal effect or higher dosages for systemic effect. Different delivery systems have a range of attributes with varying appeal to different individual women. Such a range of choices can be important for acceptability and compliance. One of the most important attributes of many newer delivery systems is the potential to deliver hormones in a controlled manner over prolonged periods of time, allowing constant low dosages, as well as constant blood and tissue levels. They also have the potential for reducing side effects and metabolic effects. Transdermal, subdermal, intravaginal and intrauterine systems are particularly likely to undergo refinement and further development in the foreseeable future with subsequent increases in popularity.

Dosage Forms↗
PubMed2005

Hormone receptor expressions and proliferation markers in postmenopausal endometrial polyps.

BACKGROUND/AIMS: Endometrial polyps are quite common in the general population, they have a significant role in postmenopausal bleeding, and the pathogenesis is unclear. The aim of this study was to investigate proliferation markers and expression of estrogen and progesterone receptors in endometrial polyps in postmenopausal women. METHODS: Endometrial polyps were removed by hysteroscopy from 36 women who presented with postmenopausal bleeding. None were using hormonal therapy. The control group consisted of 16 inactive-atrophic postmenopausal endometrial specimens removed at hysterectomy. Immunohistochemistry was used to demonstrate expression of estrogen and progesterone receptors and the cell growth and apoptosis markers, Ki67, bcl-2, c-erbB-2. RESULTS: In both the glandular epithelium and stroma of endometrial polyps, estrogen and progesterone receptors, Ki67 and bcl-2 showed significantly more positive staining than the inactive endometrium from the control group. There was no difference in expression of c-erbB-2 between the two groups. CONCLUSIONS: Estrogen may have a role in the development of postmenopausal endometrial polyps, either by direct stimulation of localized proliferation or by stimulation of proliferation via other pathways, such as activation of Ki67 or through inhibition of apoptosis via bcl-2. c- erbB-2 is unlikely to play any role in development of these lesions.

Adult↗
PubMed2005

Clinical performance and menstrual bleeding patterns with three dosage combinations of a Nestorone progestogen/ethinyl estradiol contraceptive vaginal ring used on a bleeding-signaled regimen.

OBJECTIVE: We examined the clinical performance of contraceptive vaginal rings (rings) delivering Nestorone (NES) progestin and ethinyl estradiol (EE). Ring removal times were signaled by menstrual events. Bleeding patterns, adverse events, patterns of use and continuation rates were the principal parameters evaluated. METHODS: In a two-stage 6-month trial, subjects were randomized to use rings releasing 50 microg/day of NES and either 10 (50/10) or 20 (50/20) microg/day of EE. Subjects were to keep rings continuously in situ until menstrual bleeding or prolonged spotting-signaled removal. Reinsertion was to occur 96 h later. After the randomized stage, an open-label 6-month trial of rings releasing 150 microg/day of NES and 15 microg/day of EE (150/15) began with the same menstrually signaled regimen. RESULTS: Two-hundred forty-six subjects participated in the trial. Six-month pregnancy rates ranged by ring dose from 1.3 to 3.9 per 100. For each ring dose combination, 6-month continuation rates were above 80 per 100. Bleeding and spotting (B+S) days in women with the 50 microg/day NES rings were similar in number to those experienced by cycling women not using contraception. Nevertheless, in the initial 90 days, fewer B+S days were reported by subjects with the 50/20 ring than by subjects with the 50/10 ring (p < .05). Throughout the trial, subjects using the 150/15 ring reported significantly fewer B+S episodes than did subjects with either 50 microg/day NES ring. CONCLUSION: Combined contraceptive rings used with a bleeding-signaled regimen led to few terminations attributed to bleeding problems and to acceptable continuation rates. The 150/15 ring appeared to induce fewer bleeding problems than did the lower-dose NES combination rings, but no important difference in 6-month continuation rates among the three doses was noted.

Adult↗
PubMed2005

Serum Nestorone and ethinyl estradiol levels, and ovulation inhibition in women using three different dosage combinations of a Nestorone progestogen-ethinyl estradiol contraceptive vaginal ring on a bleeding-signaled regimen.

OBJECTIVES: This trial tested the hypothesis that menstrually signaled use of contraceptive vaginal rings ("rings") releasing low-dose combinations of Nestorone (NES) and ethinyl estradiol (EE) would reliably suppress luteal activity and ovulation, and prevent unintended pregnancy, while controlling the incidence of menstrual bleeding episodes and bleeding days. METHODS: Nestorone/ethinyl estradiol rings releasing 50/10, 50/20 and 150/15 mug/day were studied through 6 months. A ring was to be used continuously, until its removal was signaled by menstrual bleeding. Reinsertion was required 96 h after removal. Serum for NES, EE and progesterone were collected and assayed, and vaginal ultrasound scans were performed in three 5-week periods to examine luteal activity, follicular growth, ovulation and their correlates. In 10 subjects using the 150/15 ring, six samples were drawn in the 24-h period after ring removal to examine serum levels of NES and EE. RESULTS: One hundred sixty subjects at three doses provided blood samples. Median serum concentrations of NES and EE demonstrated dose ratios slightly below the nominal dose ratios expected. Serum NES concentrations declined 19-22% from weeks 3 to 25. Changes in EE levels depended on dose. Nestorone levels fell 81% by 24 h after ring removal and EE levels fell by 50%. Luteal activity was completely suppressed in 94-95% of cycles and in 90% of subjects. Three pregnancies occurred in subjects participating in this serum sampling study. CONCLUSION: Satisfactory serum levels of NES and EE, and a high level of ovulation suppression were achieved. Irregular ring use, however, permitted pregnancies to occur.

Contraceptive Agents, Female↗
PubMed2005

Requirements for research investigations to clarify the relationships and management of menstrual abnormalities in women with hemostatic disorders.

This article highlights a comprehensive range of research investigations which are required to clarify the relationships between the symptom of excessively heavy menstrual bleeding and different disorders of systemic hemostasis and their management. The need for these investigations was stimulated by an international workshop involving hematologists and gynecologists with expertise and interests in these fields. The field was reviewed by a group of experts who systematically considered nomenclature, definitions, investigations, and management and identified areas of uncertainty, controversy, or absence of information. This article is an extension of those preliminary research discussions. Recommendations are made for a range of important research studies to define the nomenclature, definitions, mechanisms, clinical investigations and management of heavy menstrual bleeding in women with disorders of systemic hemostasis.

Blood Coagulation Disorders↗
PubMed2005

Comparison of three single doses of mifepristone as emergency contraception: a randomised controlled trial.

BACKGROUND: This is an analysis of the Australian component of a large World Health Organization multicentre dose-finding study of mifepristone for emergency contraception and the first clinical study of this controversial drug in Australia. AIMS: To compare the effectiveness and side-effects of three single doses of mifepristone taken within 120 h after unprotected coitus as emergency contraception. DESIGN: Double-blind, randomised controlled trial. SUBJECTS AND METHODS: One hundred fifty healthy women with regular menstrual cycles who requested emergency contraception. Participants were allocated randomly to one of the three doses (10, 50 and 600 mg). The primary outcome was confirmed pregnancy, and secondary outcome measures included side-effects and delay in the onset of the next menses. RESULTS: Pregnancy rates for mifepristone 10, 50 and 600 mg were 2.0, 2.1 and 2.1%, respectively, with no significant difference between groups. No major side-effects occurred, except an unpredictable delay in the onset of the next menses. Mifepristone 600 mg caused a significantly longer delay in the onset of the next menses than either the 10 or the 50 mg dose. CONCLUSION: Lowering the dose of mifepristone from 600 to 10 mg did not significantly impair its effectiveness as an emergency contraceptive, and caused less delay in the onset of the next menses. Therefore, a dose as low as 10 mg may be preferable to 600 mg for emergency contraception. This is very much lower than the dose required to terminate a pregnancy.

Administration, Oral↗
PubMed2004

Endometrial progesterone and estrogen receptors and bleeding disturbances in depot medroxyprogesterone acetate users.

BACKGROUND: Depot medroxyprogesterone acetate (DMPA) is a very popular hormonal contraceptive. Unpredictable bleeding disturbances are the main reasons for discontinuation and may be mediated through endometrial hormone receptors. This study was aimed to compare the expression of progesterone and estrogen receptors in the endometrium of bleeding DMPA users with that of amenorrhoeic DMPA users. METHODS: Subjects were recruited between April 2000 and January 2001. On the day of the third DMPA injection, 42 amenorrhoeic DMPA users and 42 DMPA users who had frequent or prolonged endometrial bleeding and were bleeding on that day were matched by age and body mass index. Endometrial biopsies were collected for immunohistochemical study of progesterone receptor A plus B (PRAB) and B alone (PRB) and estrogen receptor alpha (ERalpha) and beta (ERbeta) expression. RESULTS: There were 23 adequate endometrial samples from each group. There were no differences in any of a series of comparisons of PRAB, PRB, ERalpha and ERbeta expression in glands or stroma between the groups. Serum estradiol and progesterone levels were also not different between the groups. CONCLUSIONS: Endometrial PRAB, PRB, ERalpha and ERbeta expression in glands and stroma was not different between DMPA users who had frequent or prolonged bleeding and amenorrhoeic DMPA users.

Adult↗
PubMed2004

Current recommendations for the diagnostic evaluation and follow-up of patients presenting with symptomatic polycystic ovary syndrome.

Recent international agreement on the definitions of polycystic ovary syndrome (PCOS) has helped to clarify the clinical approach to diagnosis of PCOS. However, in the precise assessment of an individual patient it is still necessary for a detailed history of menstrual disorder (especially oligo- and amenorrhoea and anovulatory dysfunctional uterine bleeding), infertility or miscarriage, hyperandrogenism (mainly acne, hirsutism and scalp hair loss, distinguished from virilization) and obesity supplemented by the demonstration of polycystic ovaries on transvaginal ultrasound scanning. Assessment of endocrine changes in serum levels of luteinizing hormone, follicle stimulating hormone, oestradiol and prolactin, plus appropriate measures of circulating androgens (especially total and free testosterone, sex hormone binding globulin, 17 hydroxy-progesterone, dehydro-epiandrosterone sulphate and sometimes a 24-hour urinary free control) might help in further defining the abnormalities. Assessment of ovulatory status, obesity (body mass index and waist-hip ratio) and insulin resistance (oral glucose tolerance test with serum insulin levels) are also important in most cases. PCOS is a highly variable condition and investigation and management needs to be individualized. Long-term follow-up is also to a great extent dictated by the constellation of symptoms and clinical features of individual patients, but potential long-term hazards should be defined and patients warned of these.

Diagnosis, Differential↗
PubMed2004

The relationship of proliferating cell density at the invasive tumour front with prognostic and risk factors in human oral squamous cell carcinoma.

BACKGROUND: We hypothesise that the density of proliferating cells at the invasive tumour front (ITF) has a positive relationship with prognostic and risk factors in human oral squamous cell carcinoma (SCC). METHODS: Tissues from 47 human oral SCC specimens were collected and stained with a monoclonal antibody directed against the Ki-67 antigen using a horseradish peroxidase based two-step immunostaining method. Counting was performed on two parallel sections at the ITF using an image analyser. The Ki-67 labelling index (LI) was determined by measuring the number of nuclei/mm(2) of epithelium. RESULTS: Our results show that the density of proliferating cells is related to clinical staging, with advanced stage of disease having a significantly higher Ki-67 LI compared with early stage of disease (2111 +/- 905 vs. 1908 +/- 913; P = 0.03). Importantly, this study shows that tumours that have metastasised have a significantly higher Ki-67 LI than tumours where distant metastasis was not detected (3257 +/- 650 vs. 1966 +/- 881; P < 0.0001). CONCLUSIONS: Cell proliferation, as measured by the Ki-67 LI at the ITF, has a positive relationship with clinical staging, tumour thickness, smoking status of the patient and alcohol consumption. Further, we suggest that a multicenter study with a large cohort of patients is indicated to fully elucidate whether cell proliferation at the ITF is directly related to patient survival.

Adult↗
PubMed2003

The efficacy of non-contraceptive uses for hormonal contraceptives.

In addition to providing safe and effective contraception, both the combined oral contraceptive pill (COCP) and selected long-acting progestogen-only contraceptives have significant health benefits. The COCP may reduce menstrual blood loss, dysmenorrhoea and premenstrual syndrome; unequivocally reduces the later incidence of endometrial and ovarian cancer; appears to help protect future fertility, probably by reducing the risk of acute pelvic inflammatory disease, endometriosis and uterine fibroids. The quality of evidence for individual non-contraceptive health benefits of the COCP is very variable.

Contraceptives, Oral, Combined↗
PubMed2003

Vaginal ring delivery of hormone replacement therapy--a review.

Vaginal ring delivery systems are a highly promising approach to hormone replacement therapy (HRT). The vagina is an excellent route for steroid absorption. Menopausal vaginal rings can be designed to allow very low dose local delivery of oestrogen to the vagina for the large percentage of postmenopausal women experiencing urogenital atrophy, or can be modified to deliver much higher doses sufficient for systemic oestrogen replacement therapy, with or without simultaneous progestogen release. Clinical studies of ultra-low dose rings have shown them to be as efficacious as established treatments of urogenital atrophy (creams, pessaries) and to be preferred by most users. Pharmacokinetic and limited clinical studies of vaginal rings designed to deliver systemic doses of HRT (oestrogen alone or combined) have also been highly promising. Vaginal ring delivery of HRT offers women convenient, long-acting therapy (>/= 3 months) that is under their own personal control.

Administration, Intravaginal↗
PubMedDate not supplied

Mechanisms of abnormal uterine bleeding.

Over the past 10 years there has been an upsurge of interest in the mechanisms underlying normal and disturbed menstrual bleeding. These studies have particularly focused on the mechanisms underlying the common problems of menorrhagia associated with ovulatory and anovulatory dysfunctional uterine bleeding (DUB) and of unpredictable breakthrough bleeding during hormonal contraceptive use. A wide range of abnormalities of endometrial morphology and function have been demonstrated, but it is still not clear how all the pieces of this complex jigsaw puzzle fit together. Ovulatory DUB is predominantly associated with decreased endometrial vasoconstriction and vascular haemostatic plug formation, leading to defective control of the volume of blood which is lost during menstruation. By contrast, breakthrough bleeding is associated with a wide range of molecular disturbances which appear to result in unpredictable vessel breakdown through disturbed endometrial angiogenesis, increased vascular fragility and loss of the integrity of the endothelial, epithelial and stromal supporting structures. Anovulatory DUB is very poorly understood, but may be associated with disturbed angiogenesis, fragile vessels and defective haemostatic processes. Little is known about the actual mechanisms of the common problem of abnormal bleeding associated with specific genital tract pathologies such as uterine myomata.

Contraceptives, Oral↗
PubMedDate not supplied

Implantable contraceptives for women.

Progestogen-only implantable contraceptives are used by increasing numbers of women worldwide. This review outlines the evidence accumulated on these methods to date. Reviews of toxicological evaluations, clinical trials, endocrinological, epidemiological and social science studies, as well as operations research and economic evaluation were undertaken in preparation for an Expert Consultation convened by the World Health Organization in 2001. At the meeting, these reviews were further evaluated and the research results summarized in this consensus paper. A large body of evidence demonstrates the high contraceptive effectiveness and safety of the 5-year levonorgestrel-releasing implants Norplant and Jadelle. Information on the 3-year etonogestrel-releasing implant Implanon is more limited, but suggests that this implant has a high contraceptive effectiveness and a satisfactory safety profile. Information available on levonorgestrel-releasing implants manufactured and approved in China suggests that their clinical performance is satisfactory, but was insufficient to allow their full safety assessment. For all implants, there is insufficient information on their use by women with medical conditions. Provision of contraceptive implants requires good quality family planning services and specific provider training.

Contraceptive Agents, Female↗