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Biomedical subjects

I S Fraser

Publications and source records attributed to I S Fraser.

At least 55 records · Page 3Linked to original sources
PubMed1999

Efficacy, bleeding patterns, and side effects of a 1-year contraceptive vaginal ring.

A combined contraceptive vaginal ring designed to last 12 months was tested at three clinic sites. This ring released approximately 1 mg of norethindrone acetate (NET-Ac) and 20 micrograms of ethinyl estradiol (EE) daily. A total of 60 women were enrolled to use the ring in a schedule of 3 weeks in/1 week out. Serum norethindrone (NET) and ethinyl estradiol (EE) levels were assayed twice weekly in cycles 6, 9, and 13. Mean NET concentrations between cycles 6 and 9 were relatively stable between 13 and 19 nmol/L but showed a 10%-21% decrease in all centers between cycles 9 and 13. Mean EE concentrations ranged from 75 to 103 pmol/L, but did not have the same decrease as NET between cycles 9 and 13. Cycles with progesterone peaks (> 9.6 nmol/L) compatible with some luteal activity occurred in 4% of cycles sampled in Sydney, 3% in Santo Domingo, and 26% in Los Angeles. Half of these cycles exhibited at least one progesterone value > 32 nmol/L with three of 18 occurring in noncompliant cycles. Heavier body weight was associated with increased probability of luteal activity. Based on serum estradiol peaks > 400 pmol/L, eight of 81 cycles appeared to have marked follicular activity with no luteal activity. No pregnancies occurred. Nausea was reported by about half the subjects in approximately 10% of the visits (mainly in the first 1-2 days in the first cycle immediately after ring insertion). Vomiting was reported by 20% of subjects early in the first cycle only. Headache was reported on occasion by nearly 50% of the women, but the relationship to ring use was uncertain. Vaginal discharge was reported by 17 women (82% of these were from one clinic). Of 60 women, 14 discontinued before completing the study, but only two discontinuations were for medical reasons. Small but statistically significant changes occurred in lipid levels in two of the three centers. All changes remained within normal limits and were similar to those seen with many oral contraceptives. It appears that this ring may perform slightly differently in different populations, but is a highly satisfactory method of contraception for many women. Minor modifications in design could provide higher levels of steroid release and in the later months of the ring life span would assure continuing high levels of contraceptive protection for heavier women.

Adolescent↗
PubMed1999

A comparative study of two contraceptive vaginal rings releasing norethindrone acetate and differing doses of ethinyl estradiol.

Two combined contraceptive vaginal rings (CVR) each releasing approximately 1 mg norethindrone acetate (NET-Ac) and either 20 micrograms or 15 micrograms ethinyl estradiol over 24 h were tested at three clinic sites in Los Angeles, San Francisco, and Sydney. A total of 61 women were enrolled to use the ring on a schedule of 3 weeks in/1 week out for four treatment cycles. Serum estradiol, progesterone, norethindrone (NET), and ethinyl estradiol (EE) levels were assayed twice weekly in all four treatment cycles. Both CVR performed well, with no pregnancies occurring and only one cycle of luteal activity suggestive of ovulation (serum progesterone > 32 nmol/L) occurring with each ring (0.9% of cycles with the 1/15 ring and 1.2% of cycles with the 1/20 ring). Although there was significantly more luteal activity in women using the 1/15 CVR (5.9% compared with 1.2% of cycles), only three cycles with a marked degree of luteal activity (progesterone > 10 nmol/L) occurred among compliant women. Serum levels of NET and EE were consistently elevated during use of both rings. There was no significant difference between serum levels with the two rings because of wide interindividual variations, although both NET and EE levels tended to be higher with the 1/20 ring. However, there was a significant difference in EE levels between the women in Los Angeles and Sydney using the same dose rings. Total cholesterol, HDL, and LDL cholesterol values were not significantly changed during treatment. Triglycerides increased but remained within the normal range. Overall cycle control was good with both formulations, but there was slightly more cycle disturbance with the lower dose ring. There was no change in mean body weight during the study, and individual weight changes appeared to be idiosyncratic. Side effects were infrequent and similar to those reported with other steroidal contraceptive methods. Three women complained of vaginal discharge, one with accompanying itch and one with a vaginal Candida infection in cycle 1. Overall, both of these EE/NET-Ac rings performed well, with only minor and mainly nonsignificant differences in effect on serum EE, NET, E2, and progesterone levels and lipids, and on vaginal bleeding patterns.

Adolescent↗
PubMed1999

Bleeding arising from the use of exogenous steroids.

A range of hormonal contraceptives and hormone replacement therapies are widely and increasingly used in most societies. These preparations result in a wide variety of scheduled and unscheduled effects on uterine bleeding patterns, some of which may be quite disconcerting for the women who use them. There is now an extensive literature on the analysis of these bleeding patterns, the way in which different hormonal methods affect these patterns and the influence which they may have on women's choice to continue or discontinue use of a method. This review has concentrated particularly on the issues related to bleeding patterns with hormonal contraceptives, but many of the issues are also relevant to menopausal hormone replacement therapy. This is particularly the case with research into the complex vascular and molecular mechanisms underlying disturbances of bleeding, where there may well be substantial overlap. Perception and tolerance are important in determining a woman's approach to a change in her menstrual pattern, and her possible acceptance of counselling and treatment approaches which may improve her symptoms.

Contraceptives, Oral, Hormonal↗
PubMed1999

Changes in vascular basement membrane in the endometrium of Norplant users.

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 (+/- SEM) of 189.6 +/- 7.0 vessels/mm2 during the control cycle to 253.9 +/- 80.7 vessels/mm2 at 2-13 weeks of Norplant exposure, and to 212.7 +/- 12.9 vessels/mm2 at 14-42 weeks. During the control cycle, a mean of 161.4 +/- 4.5 vessels/mm2 stained for collagen IV (85% of all vessels), while at 2-13 weeks, 144.5 +/- 13.0 vessels/mm2 stained for collagen IV (57% of all vessels) (t ratio = 2.08, P = 0.0057). By 14-42 weeks, 71% of vessels (151.0 +/- 9.8) vessels/mm2 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 +/- 4.2 vessels/mm2 in the control cycle (93% of vessels), to 156.3 +/- 6.7 vessels/mm2 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 +/- 9 vessels/mm2 (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 +/- 3.0 vessels/mm2 during the control cycle (31% of vessels) to 43.6 +/- 5.6 vessels/mm2 (only 17% of vessels) at 2-13 weeks (t ratio = 2.08, P = 0.025). At 14-42 weeks, only 19% of vessels stained for HSPG (41.3 +/- 5.8 vessels/mm2; t ratio = 2.04, P = 0.009).

Adolescent↗
PubMed1999

Investigation of a unique male and female sibship with Kallmann's syndrome and 46,XX gonadal dysgenesis with short stature.

A sibship is described where the brother and a sister both have Kallmann's syndrome (anosmia and deficiency of gonadotrophin releasing hormone) and the woman also has streak ovaries. Although there are several conditions that may occur with Kallmann's syndrome, there are no known reports of ovarian dysgenesis being associated with this disorder. Cytogenetic analysis showed no rearrangement or major deletions of the chromosomes. Linkage analysis using informative microsatellite markers predicts that a gene other than KAL1 (at Xp22.3) is implicated in the Kallmann's syndrome manifesting concurrently with ovarian dysgenesis found in this family.

Adult↗
PubMed1999

Variations in vaginal epithelial surface appearance determined by colposcopic inspection in healthy, sexually active women.

A total of 107 sexually active women, aged 18-35 years, was recruited through family planning clinics in four centres in different countries. Each woman underwent two or three gentle but thorough and systematic vaginal inspections using a consistent technique with colposcopic magnification over a 4-6 month period to look for changes in vaginal and cervical appearance which might be related to sexual intercourse, tampon use, contraceptive method used, cigarette smoking or other environmental factors. Obvious changes in appearance were photographed at x10 magnification. These 'appearances' or 'conditions' were classified according to a modification of the recommendations of a workshop sponsored by the World Health Organization, the Population Council and the Conrad Program. Most of these alterations in the appearance of the vaginal epithelium were judged to be of such minor clinical importance that they have been termed 'conditions' or 'changes in appearance' rather than 'lesions'. In all, 56 'conditions' or 'appearances' were noted in 314 inspections, the commonest being petechiae (53.6%). Potentially significant conditions justifying the term 'lesions' (three microulcerations, two ecchymoses, five abrasions and one mucosal tear; 3.5% of inspections) usually healed spontaneously and disappeared rapidly. The incidence of these conditions was highest when the inspections followed intercourse in the previous 24 h (25.2 versus 14.2%; P < 0.0008), or tampon use (32.4 versus 15.9%; P < 0. 0001). These processes may be regarded as a reflection of regular minor trauma to the vaginal epithelium.

Adolescent↗
PubMed1999

Endometrial lysosomal enzyme activity in normal cycling endometrium.

The objective of this study was to evaluate the possible role of four lysosomal enzymes in endometrial function and remodelling during the normal menstrual cycle by fluorimetric measurement (acid phosphatase, N-acetyl-beta-D-glucosaminidase, alpha-L-fucosidase and alpha-D-mannosidase). A prospective study was conducted of 45 endometrial biopsies obtained from women with normal menstrual cycles. Activity of all four enzymes was identified in human endometrium. Activity of acid phosphatase and N-acetyl-beta-D-glucosaminidase was relatively high, whilst that of alpha-L-fucosidase and alpha-D-mannosidase was low. There was no significant change in the activity of any of the four enzymes from the proliferative to the secretory phase of the cycle. This study suggests that the activity of these enzymes remains constant throughout a major portion of the normal cycle.

Acetylglucosaminidase↗
PubMed1999

Regulating menstrual bleeding. A prime function of progesterone.

Progesterone plays a crucial role in the coordination of endometrial breakdown as well as in the determination and regulation of menstrual blood loss and endometrial transudation of fluid. Furthermore, long-term exposure of the endometrium to progesterone can result in abnormal angiogenesis. Although additional investigations of the estrogen-progesterone relationship are needed, the relative concentrations of these two hormones appear to have important effects on bleeding patterns. Current research is aimed at greater understanding of the ways in which these two hormones interact with several complex cellular and metabolic mechanisms to regulate endometrial bleeding.

Endometrium↗
PubMed1998

Use of systematic reviews of randomised trials by Australian neonatologists and obstetricians.

OBJECTIVE: To determine what proportion of Australian neonatologists and obstetricians report using systematic reviews of randomised trials. DESIGN: Cross-sectional survey using structured telephone interviews. SETTING: Australian clinical practice in 1995. PARTICIPANTS: 103 of the 104 neonatologists in Australia (defined as clinicians holding a position in a neonatal intensive care unit); a random sample of 145 members of the Royal Australian College of Obstetricians and Gynaecologists currently practising in Australia. MAIN OUTCOME MEASURES: Information sources used in clinical practice; reported awareness of, access to and use of systematic reviews, and consequent practice changes. RESULTS: Response rates were 95% (neonatologists) and 87% (obstetricians); 71 neonatologists (72%) and 55 obstetricians (44%) reported using systematic reviews, primarily for individual patient care. Databases of systematic reviews were used with a median frequency of once per month. Among neonatologists, systematic reviews were used more commonly by those who were familiar with computers, attended professional meetings, and had authored research papers. Among obstetricians, they were used more commonly by those who were familiar with computers, had less than 10 years' clinical experience, attended more deliveries, and were full-time staff specialists in public hospitals. Of neonatologists who reported using systematic reviews, 58% attributed some practice change to this use. For obstetricians, the corresponding figure was 80%. CONCLUSIONS: There is evidence that Australian neonatologists and obstetricians use systematic reviews and modify their practice accordingly. Dissemination efforts can benefit from knowledge of factors that predict use of systematic reviews.

Adult↗
PubMed1998

Norplant consensus statement and background review.

This review has highlighted the attributes of a very important new method of contraception. The signatories to this document agree that, with the provision of appropriate information and instruction for the user, Norplant is a good contraceptive choice to be made available worldwide in family planning programs that have the resources for appropriate training and counseling. The signatories to this document are acting in their own personal capacity and not as representatives of any particular organization.

Contraceptive Agents, Female↗
PubMed1998

Precise measurements of intrauterine vascular structures at hysteroscopy in menorrhagia and during Norplant use.

Using currently available equipment for panoramic hysteroscopy, the size of images viewed cannot be accurately judged because of the magnifying and distorting effects of the objective lens. This study has demonstrated that magnification by the hysteroscope lens can alter the apparent size of images by up to 27%. An additional effect of lens distortion can alter the apparent size of images viewed by up to 28%, depending on the position of the image in the field of view. These effects are independent and may be additive. Thus, the apparent size of intrauterine structures at hysteroscopy may bear little resemblance to their actual size. Image-correction methods are described which reduce the effects of image magnification on the apparent size of an object viewed through the hysteroscope to 7%, and the effect of distortion to 3 %. This technique can greatly improve the accuracy of measurement at hysteroscopy, and has been utilized in this study for the precise measurement of superficial endometrial vascular diameter (mean+/-SEM) in 34 Norplant users (120+/-11.6 microm) and 20 women with spontaneous menorrhagia (74+/-7.2 microm). It has also confirmed the presence of scattered dilated vessels (up to 777 microm in diameter) on the endometrial surface in some Norplant users.

Adolescent↗
PubMed1997

Effect of different insertion regimens on side effects with a combination contraceptive vaginal ring.

The study population included 159 women aged 18 to 37 years requiring contraception (60 in Sydney, 99 in Los Angeles). The design consisted of a 6 month study of a contraceptive vaginal ring (CVR) releasing 20 micrograms ethinyl estradiol and 1 mg of norethindrone acetate daily over two successive cycles with a new ring on each of three different insertion regimens. A total of 831 woman-months of exposure were recorded, and 129 women completed the study. The overall incidence of side effects was similar in the two centers and differences between the insertion regimens were not observed. Transient nausea following insertion of a new ring (mainly lasting 0.5 to 48 h) was the most prominent side effect, with no significant difference between the insertion regimens (although the incidence tended to be highest with bedtime insertion [34%] and lowest with early evening insertion and temporary removal during the first night [27%]). Transient vomiting occurred in about 10% of women in the first 24 h after first insertion of a new ring. The incidence and severity of nausea was greatly reduced in cycle 2 with each regimen (6% to 9% of women). Nausea could be prevented by overnight soaking of the ring in water before use. Other side effects such as headache, dizziness, uterine cramps, breakthrough bleeding, weight gain, and ring expulsion occurred with similarly low frequency in all three insertion groups. One pregnancy occurred with probable ovulation between cycles 5 and 6, the only pregnancy recorded to date in studies with this ring. The study demonstrated that this effective and generally well tolerated CVR causes a relatively high incidence of transient nausea after insertion of a new ring, which is probably due to accumulation of ethinyl estradiol on the ring surface during storage. Acceptability is still high, and this particular CVR merits further development.

Adult↗
PubMed1997

Colposcopic evaluation of a vaginal gel formulation of iota-carrageenan.

There is an urgent need to develop safe, effective, and acceptable vaginal products for the prevention of sexually transmitted infections. Preliminary in vitro results suggest that vaginal formulations of sulfated polysaccharides, including iota-carrageenan, have the potential to block mucosal transmission of human immunodeficiency virus (HIV). Twenty-five women in five sites participated in Phase I trials to evaluate the safety of a formulation containing iota-carrageenan (PC 213). The results of this study indicate that a 5 mL 2% gel formulation of iota-carrageenan is not associated with significant irritation of the female reproductive tract when administered once daily in the absence of sexual intercourse. Given the small number of participants in this initial study, careful observation for potential irritation must also be included in larger studies of this and other vaginal formulations.

Administration, Intravaginal↗
PubMed1996

Depot goserelin and danazol pre-treatment before rollerball endometrial ablation for menorrhagia.

OBJECTIVE: To compare the safety and efficacy of a GnRH agonist, depot goserelin, and danazol as preoperative treatments before rollerball endometrial ablation. METHODS: We performed an open, randomized study of women with clinically convincing histories of menorrhagia. Two treatment groups of equal size (goserelin acetate, 3.6 mg subcutaneous implant given monthly, n = 30; and danazol, 200 mg two times per day, n = 30) were treated for 2 months before undergoing endometrial ablation, which entailed using the rollerball with 80-100 watts of coagulating current. RESULTS: Measured menstrual blood loss decreased dramatically after ablation, with 74% of goserelin users and 62% of danazol users achieving complete amenorrhea by the end of the 6-month follow-up period. Among women who did not achieve complete amenorrhea, those in the danazol group were more likely to experience occasional episodes of moderate or heavy bleeding. Mean measured blood loss decreased from 94.8 to 1.1 mL at 3 months and 1.0 mL at 6 months after goserelin, and 97.9 to 15.0 mL and 7.4 mL after danazol. Menstrual pain also improved markedly. The median duration of surgery was 20 minutes (range 5-55) in both groups, median irrigation fluid deficit was 100 mL (range 0-800), and median operative blood loss was 20 mL (range 1-50). Endometrium was less than 2 mm thick in all goserelin and most danazol users. Side effects of goserelin and danazol therapy were all within the expected pattern for these drugs. CONCLUSION: Depot goserelin and danazol both provide adequate endometrial preparation before rollerball endometrial ablation for treatment of menorrhagia due to ovulatory dysfunctional uterine bleeding.

Combined Modality Therapy↗
PubMed1996

Medium-term follow-up of women with menorrhagia treated by rollerball endometrial ablation.

OBJECTIVE: To assess the medium-term efficacy of rollerball endometrial ablation. METHODS: From January 1990 to December 1993, 142 women underwent rollerball endometrial ablation for menorrhagia, most with ovulatory dysfunctional uterine bleeding. Each was sent a detailed questionnaire 12-52 months later and then followed-up, with an overall 93% response rate. Thirty-two had uterine myomas (13 with hysteroscopic myoma resection) and 11 had a large endometrial polyp (four with both). Most of the women were pretreated with danazol. RESULTS: Thirty-two of 128 (25%) achieved long-term, complete amenorrhea and only three eventually resumed their periods after prolonged amenorrhea. Four women experienced late amenorrhea, which was probably due to menopause. The percentage of satisfactory outcomes decreased gradually with time (95.5, 85.5, and 75% for 13-24, 25-36 and more than 36 months respectively; P = .051); this was not statistically significant. One hundred twenty-one patients (85.2%) did not need further surgical treatment. The incidence of repeat ablation (8.5%) and hysterectomy (8.5%) increased gradually with time over the first 3 years but not thereafter, although total numbers are still small. Cyclic pelvic pain and premenstrual symptoms were much improved in both short and long term. Most women remained satisfied with the operation (84%) and would recommend it to others (89%). CONCLUSION: Rollerball endometrial ablation is a simple, effective, and acceptable procedure for the management of intractable menorrhagia due to ovulatory dysfunctional uterine bleeding. However, with the findings of slightly less satisfactory results with time, longer-term follow-up is still needed to establish the ultimate effectiveness of the procedure using different techniques.

Adult↗
PubMed1996

A comparison of mechanisms underlying disturbances of bleeding caused by spontaneous dysfunctional uterine bleeding or hormonal contraception.

Recent research has not been able to demonstrate close endometrial morphological correlations with specific abnormalities of menstrual bleeding, but has pointed to an increasing number of molecular mechanisms that may be involved in the occurrence of certain forms of abnormal uterine bleeding. Ovulatory and anovulatory dysfunctional uterine bleeding (DUB) and progestogen-related breakthrough bleeding (BTB) are three conditions with quite different clinical characteristics. It is also probable that the local endometrial molecular mechanisms associated with these three menstrual disturbances are quite different. Ovulatory DUB is associated with a series of vascular and haemostatic disturbances that all appear to contribute to increased loss of blood and tissue fluid at menstruation. Anovulatory DUB is associated with obvious disturbances of endometrial histology, vascular morphology and fragility, with variable and increased blood flow. Progestogen-related BTB is associated with a multitude of morphological and functional endometrial changes that appear to relate predominantly to a patchy capillary origin for the bleeding. Many molecular and cellular changes have been observed in all three conditions. It is not yet known whether there is a single, but different, underlying mechanism responsible for these multiple abnormalities in each of the three clinical situations.

Anovulation↗