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Biomedical subjects

I S Fraser

Publications and source records attributed to I S Fraser.

At least 73 records · Page 4Linked to original sources
PubMed1996

Effects of high dose progestogens on white cells and necrosis in human endometrium.

Endometrium was collected from 20 high-dose progestogen-treated patients and examined for leukocyte populations by immunohistochemistry and phloxine-tartrazine staining. A labelled streptavidin-biotin-alkaline phosphatase technique was used with antibodies against leukocyte common antigen (LCA), T cells (CD3), neutrophils (NP57), macrophages] (CD68, KP1) and B cells (CD20). The numbers of LCA (1070 +/- 117/mm2), CD3 (459 +/- 60/mm2), CD68 (129 +/- 21/mm2) positive cells and endometrial granulated lymphocytes (EGL) (236 +/- 41/mm2) were significantly higher than those in the control group (P < 0.001). Of these, EGL increased most (6.7 times). NP57 positive (NP57+) neutrophils were present in five out of 20 progestogen-treated samples and NP57 negative (NP57-) neutrophils in another six out of 20; while a neutrophil was only identified in one control tissue (P = 0.002). Three progestogen-exposed endometrial samples had either focal or extensive necrosis, and many NP57+ and NP57- neutrophils were present in the necrotic areas. EGL, neutrophils and macrophages are known to release a number of cytolytic and cell toxic molecules which may play a role in the initiation or acceleration of progestational endometrial necrosis.

Antigens, CD↗
PubMed1996

Microvascular density in conditions of endometrial atrophy.

Irregular menstrual bleeding in users of hormonal contraception represents the single major reason for discontinuation of these contraceptive methods. The mechanisms which underlie these bleeding disturbances are poorly understood, but appear to be associated with changes in the endometrial microvasculature following abnormal patterns of sex steroid exposure. Endometrial microvascular density is known to be increased in users of the low-dose levonorgestrel contraceptive implant, Norplant. This study explores microvascular density in other conditions of spontaneous (post-menopausal) and induced (danazol and goserelin) endometrial atrophy. Endometrial biopsies were fixed, paraffin-embedded and sections were immunostained using anti-CD34 antibody to identify vascular endothelial cells. The mean microvascular density (+/-SEM) for control samples was 186 +/- 8 vessels/mm2. There were no statistically significant changes in vascular density observed across the menstrual cycle. Mean microvascular density in spontaneous and induced endometrial atrophy did not differ significantly from that observed in the control population. The mean microvascular density was 230 +/- 17 vessels/mm2 in 31 postmenopausal women, 269 +/- 67 vessels/mm2 in 25 subjects treated with danazol was and 191 +/- 45 vessels/mm2 in nine subjects treated with goserelin. These findings suggest that the mechanisms controlling microvascular density in conditions of endometrial atrophy may vary according to the nature of the atrophic stimulus.

Adult↗
PubMed1996

Lack of skin test reactivity to common mycobacterial antigens in human immunodeficiency virus infected individuals with high CD4 counts.

BACKGROUND: T cell response to mycobacterial antigens may be directed against those antigens common to all mycobacteria (group i), those restricted to slow (group ii) or fast growers (group iii), or those which are species- or subspecies-specific (group iv). These responses were assessed by skin testing patients infected with the human immunodeficiency virus (HIV) and healthy controls with reagents derived from different strains of mycobacteria. METHODS: Skin test responses to new tuberculins prepared from Mycobacterium tuberculosis, M avium serotypes 4 and 8, and either M intracellulare or M flavescens antigens were evaluated prospectively in 51 HIV infected patients and 67 healthy controls. RESULTS: Assessment of induration at 72 hours showed absence of skin test response to common mycobacterial antigens in all 27 HIV positive patients with CD4 counts of > or = 400/mm3 (range 400-1594, median 540) compared with 27% reactivity in controls; complete anergy was demonstrated in 24 patients with CD4 counts of < 400/mm3. By contrast, no difference in species or subspecies-specific responses was found between healthy controls and HIV positive patients with CD4 counts of > or = 400/mm3. CONCLUSIONS: Subsets of CD4+ T helper cells are instrumental in determining the balance between cell-mediated and humoral immunity. One T helper subset (TH1) produces cytokines that increase cellular immunity and is stimulated by group i common mycobacterial antigens. Lack of this response, but preservation of responses to species-specific antigens while CD4 counts are near normal, may indicate an early failing of TH1 immunity and explain the increased susceptibility of HIV positive patients to mycobacterial infection early on in the evolution of their HIV infection.

Adolescent↗
PubMed1995

Emergency contraception. General practitioner knowledge, attitudes and practices in New South Wales.

OBJECTIVES: To assess the knowledge, attitudes and practices of general practitioners in New South Wales regarding the provision of emergency contraception. DESIGN: Randomised group comparison of 100 rural and 100 urban general practitioners (GPs) by questionnaire. RESULTS: Eighty-four rural and 76 urban GPs responded. More rural GPs were knowledgeable about emergency contraception than urban GPs (95% v. 78%), and more women knew about it than men. More urban GPs frequently prescribed emergency contraception than rural GPs (26% v. 6%) and female GPs prescribed it more readily than male GPs (22% v. 12%). There was great variation in the regimens prescribed, especially among rural GPs. Twenty-five per cent of urban GPs and 31% of rural GPs did not offer women information about emergency contraception, while 16% of both groups included such information in any discussion about contraceptive options, and 18% gave information only if requested by the woman. More than 60% of the GPs would provide information about emergency contraception as a back-up to use of barrier methods. CONCLUSIONS: The sex, attitude and knowledge of the GPs influence the likelihood of women being made aware of or being given emergency contraception in NSW. There is a need to further educate both the public and practitioners about emergency contraception.

Attitude of Health Personnel↗
PubMed1995

The acceptability of a combined oestrogen/progestogen contraceptive vaginal ring.

The acceptability of a vaginal ring releasing ethinyl oestradiol 20 mcg per day and norethindrone acetate 1 mg per day was assessed during a six-month phase II trial comparing three different regimens, which was carried out simultaneously in Los Angeles and Sydney. Sixty women were enrolled in Sydney and 90 in Los Angeles. On admission into the study, the women were asked to complete a questionnaire which gave details of age, last contraceptive method used, contraceptive methods used in the past and their reason for liking or disliking previous contraceptive methods, as well as their reason for stopping the last method. On completion of the study or leaving the study for any reason, each woman was asked to complete an acceptability questionnaire which included her experiences with the ring and the rating of the method. The responses to these two questionnaires form the basis of this report. The overall rating of the ring was similar in both the Sydney and Los Angeles groups. Sixty-nine percent of women rated the method as very good. Seventy-two percent of women in Los Angeles and 62% of women in Sydney liked the ring much more than their most liked previous method. In both groups the method they liked best apart from the ring was the pill (62% in Sydney and 53% in Los Angeles). The major reasons for liking the ring were convenience of use, effectiveness and no requirements for taking medication daily. Most women in both studies would recommend the ring to others (92% in Sydney and 89% in Los Angeles).

Adolescent↗
PubMed1995

Endometrial morphometry in users of intrauterine contraceptive devices and women with ovulatory dysfunctional uterine bleeding: a comparison with normal endometrium.

Copper-bearing intrauterine contraceptive devices (IUCD) are commonly associated with menorrhagia. They cause certain morphological changes in the endometrium. These have been extensively reported and the mechanisms of menorrhagia have been investigated in a number of studies. By contrast, ovulatory dysfunctional uterine bleeding has not been as widely studied and mechanisms of menorrhagia in these patients are still not well understood. In this study, we examined endometrial morphometry in a group of women using IUCD, a group of women with ovulatory dysfunctional bleeding, and a control group of women with entirely normal cycles. There was increased leukocytic infiltration of the endometrium in both groups of women with menorrhagia compared to control cases. In addition, IUCD use was associated with greater luteal phase glandular epithelial height, supporting the concept of a secretory function defect in glandular epithelium. Possible links are postulated between static morphometric observations and dynamic biochemical changes.

Australia↗
PubMed1995

Pregnancy in women with Kallmann's syndrome.

OBJECTIVE: To induce of ovulation and pregnancy in women with Kallmann's syndrome. DESIGN: Retrospective study. PATIENTS: Three women with hypogonadotropic hypogonadism and anosmia with a desire for pregnancy. INTERVENTIONS: Investigation of hypothalamic-pituitary-ovarian function and induction of ovulation by pulsatile GnRH or intramuscular human pituitary gonadotropins (hPG) or hMG with hCG. MAIN OUTCOME MEASURES: Successful induction of ovulation as measured by serum P levels and successful pregnancy. RESULTS: Ovulation was induced successfully in all three patients on more than one occasion and nine pregnancies occurred. Gonadotropin-releasing hormone was given IV by an electronically timed syringe driver. A total of 12 pulsatile GnRH cycles resulted in two pregnancies, 6 of these cycles being in one patient who did not ovulate or conceive with this therapy. Ovulation occurred in 10 of 16 hMG or hPG cycles, with conception in 7 of these. Gonadotropin usage was higher in these women compared with women with hypogonadotropic hypogonadism without anosmia (2,850 compared with 2,100 IU per treatment cycle), and the follicular phase was longer. CONCLUSIONS: All three women conceived and had children after induction of ovulation. The success rate of these therapies in Kallmann's syndrome appears to be high in spite of very few reports in the literature.

Adolescent↗
PubMed1995

Angiogenic activity in normal and dysfunctional uterine bleeding human endometrium; as measured by the chick chorioallantoic membrane assay.

The modified chick chorioallantoic membrane assay was used to measure the angiogenic activity of whole human endometrium, endometrial gland and endometrial stromal cell preparations. Specimens were studied from normal subjects and from those suffering from dysfunctional uterine bleeding. This was done in order to investigate possible sites of angiogenic factor synthesis in endometrium. Significant angiogenic activity was demonstrated in all three sites and was present in all phases of the cycle except for the late secretory phase specimens. In the late secretory phase, compared to the controls, there was no significant angiogenic activity in the whole endometrial, endometrial gland nor endometrial stromal cell preparations. There were no differences in angiogenic activities between the various phases studied apart from a significant decrease in angiogenic activity for the endometrial gland cell preparations between the midsecretory phase and the late secretory phase. This study suggests than human endometrium produces local angiogenic factors throughout the menstrual cycle and that these factors may decrease towards the end of the cycle. It has been suggested that dysfunctional uterine bleeding may be due to disturbances in local angiogenic factors produced in the endometrium. This study found no significant differences in angiogenic activities between normal endometrium and dysfunctional endometrium. This suggests that dysfunctional uterine bleeding may not be due to disturbances in local angiogenic factors.

Animals↗
PubMed1995

The effect of high-dose medium- and long- term progestogen exposure on endometrial vessels.

A total of 19 paraffin-embedded endometrial tissue blocks were obtained from high-dose progestogen-exposed patients. A labelled streptavidin-biotin-alkaline phosphatase method was used with antibodies against von Willebrand factor (vWF) and CD34. The density of CD34 and vWF positive (CD34+ and vWF+) vessels in progestogen-exposed endometria (103 +/- 9.6/mm2 and 106 +/- 8.7/mm2) was significantly lower than in endometria from women with normal cycles (169 +/- 9.3/mm2 and 136 +/- 8.0/mm2) (P < 0.05). In women with normal menstrual cycles the concentration of CD34+ vessels was significantly higher than the number of vWF+ vessels (P = 0.0001). By comparison, the concentration of CD34+ vessels was similar to the concentration of vWF+ vessels in progestogen-exposed endometria. The ratios of vascular density as determined by vWF+ and CD34+ staining the control and progestogen groups were 0.81 and 1.05 respectively (P = 0.0001). Dilated venules were seen in the progestogen group. This study has demonstrated firstly that CD34 antibody detected the endothelial cells in a higher proportion of small endometrial vessels than vWF, and secondly that high-dose progestogen exposure significantly decreased the density of microvessels and increased the number of dilated venules in endometrium.

Antigens, CD↗
PubMed1995

The effects of natural and synthetic sex steroids on human decidual endothelial cell proliferation.

The effects of natural and synthetic sex steroids on the proliferation of human decidual capillary endothelial cells in culture were investigated. Oestradiol at 5.0 ng/ml stimulated culture growth. Lower concentrations of oestradiol inhibited growth, while higher concentrations had no effect. Low concentrations of progesterone (5.0 and 10.0 ng/ml) had no effect on growth, while higher concentrations (20.0 and 40.0 ng/ml) inhibited growth. Combinations of oestradiol and progesterone usually reproduced the effects of progesterone alone. 3-Ketodesogestrel and levonorgestrel both inhibited endothelial cell growth, while medroxyprogesterone acetate had no effect. These findings suggest that (i) oestradiol and progesterone have direct effects on endothelial cells and are probably involved in the cyclical growth and regression of endometrial blood vessels in vivo, and (ii) the actions of certain progestogen-only contraceptives may have direct effects on endometrial blood vessels.

Capillaries↗
PubMed1995

Effects of progestogens on human endometrium.

The effect of progestogens on endometrium depends on the dosage, duration of exposure, the type of progestogen, and the presence or absence of estrogen. Mechanisms of progestogen action in endometrium are mainly expressed through the binding of hormone to specific nuclear receptors. Exogenous progestogens seem to influence the hypothalamic-pituitary-ovarian-endometrial axis differently in different individuals. Endogenous hormones resulting from ovarian secretion have effects on the endometrium independent of, and in combination with, exogenous progestogens. Endometrial morphological changes with progestogens vary from suppression of endometrial glandular growth, through stromal decidualization and leukocytic infiltration to glandular atrophy and stromal focal necrosis. In a minority of cases resulting from very prolonged treatment connective tissue fibers increase to some degree and may be accompanied by endometrial fibrosis and calcification. Clinical and histological data have demonstrated that all these changes, including fibrosis and calcification, return to normal in a short period after discontinuing treatment. Endometrial changes during progestogen therapy are often accompanied by leukocyte infiltration, especially when necrosis occurs. White blood cells constitute an important component of normal endometrium. The number and the type of leukocytes change during the normal menstrual cycle apparently related to circulating ovarian hormonal changes. Exogenous progestogens also influence white blood cells, by increasing total numbers and certain specific cell types. Changes in endometrial white blood cell function as a consequence of exogenous progestogens are unclear, but it is possible that the increase of leukocyte infiltration resulting from exogenous progestogens plays an important role in evoking progestational endometrial necrosis.

Cell Movement↗
PubMed1994

Depo-Provera use in an Australian metropolitan practice.

OBJECTIVE: To review the characteristics and experience of Australian women treated with depot medroxyprogesterone acetate (DMPA) in one gynaecological practice in Melbourne since 1973. DESIGN: A detailed retrospective review of clinical data on 363 women treated with a total of 2298 injections of DMPA over the past 20 years. RESULTS: The main indication was contraception, although a substantial minority (20%) were treated with DMPA predominantly for medical indications such as endometriosis. No pregnancy occurred within three months of an injection. There was also high acceptability, with a mean of 6.3 injections per subject, and a mean overall follow-up of 43.3 months. The median delay in the return of fertility in those wishing to conceive immediately was 9.2 months. Only one patient complained of difficulty in conceiving. Menstrual bleeding disturbances only led to 7.3% of the discontinuations, although fairly frequent use of short courses of oral oestrogen (in 40% of women) was employed in the early months of DMPA treatment. Other side effects were relatively infrequent, the most common being superficial dyspareunia or reduced libido (in 8%). CONCLUSIONS: This much maligned drug merits a legitimate place among the contraceptive choices available for Australian women. Accurate, unbiased information about the extensive worldwide experience needs to be made available to all Australian medical practitioners.

Adolescent↗