Biomedical subjects
Publications and source records attributed to D L Healy.
The combination of RU486 (mifepristone) and prostaglandin analogues has been used for medical abortion in several European centres. We surveyed 41 Australian women who successfully used this method of abortion in a World Health Organization-sponsored trial. Overall, the women were satisfied with the method and found the associated pain level acceptable.
OBJECTIVE: To compare the cost of laparoscopically assisted vaginal hysterectomy (LAVH) with that of total abdominal hysterectomy (TAH) under casemix. DESIGN: Retrospective comparison of the costs, operating time and length of hospital stay. PATIENTS: The 16 women undergoing consecutive LAVH and 16 age-matched women undergoing TAH between 1 February 1994 and 31 July 1995; all women were public patients undergoing hysterectomy for benign disease. SETTING: Monash Medical Centre, a large tertiary teaching hospital in Melbourne, Australia, where casemix is used to determine funding and budget allocation. RESULTS: The difference between the costs of the two procedures was not statistically significant (P = 0.5), despite the cost of laparoscopic hysterectomy including that of disposables. The mean operating time for TAH was 86 minutes (95% CI, 65.5-106.5), compared with 120 minutes (95% CI, 100.8-140.5) for LAVH (P < 0.01). The mean length of stay in the TAH group was 5.75 days, compared with 3.25 days in the LAVH group (P < 0.001). CONCLUSION: In hysterectomy for benign gynaecological disease, the laparoscopic procedure costs the same as the total abdominal procedure. Audit such as this is important in patient management and in guiding hospitals in funding and bed allocation.
To evaluate the efficacy of gamete intra-Fallopian transfer (GIFT) the Kaplan-Meier life table method was used to analyse a patient cohort treated with GIFT between 1991 and 1994. In a tertiary referral centre for reproductive medicine, 1628 women with a median age of 33 years and various causes of infertility were included to calculate cumulative pregnancy and live birth rates. Age and cause of infertility were main factor variables and the study was based on a total of 2941 consecutive GIFT cycles, leading to a first clinical pregnancy, and 3052 cycles, leading to a first live birth. The cumulative pregnancy and live birth rates were 49.6 and 38.8% respectively, after three initiated cycles and 64.1 and 52.0% respectively, after five initiated cycles. The multiple pregnancy rate was 22.6%. The implantation rate of 13.1% after GIFT demonstrates that the developing embryo benefits from a period of exposure within the environment of the Fallopian tube. The present results indicate that approximately 50% of couples will have at least one live baby after five initiated GIFT cycles. Advancing age was a major negative prognostic factor for the cumulative live birth rate because of higher cancellation rates, lower implantation rates and higher pregnancy failure rates.
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.
BACKGROUND AND OBJECTIVE: We have previously reported elevated serum immunoreactive inhibin (INH) levels in patients with ovarian malignancies, particularly granulosa cell and mucinous tumours. The present study was designed to compare INH measurements using a heterologous radioimmunoassay with cross-reactivity for inhibin alpha-subunit derived peptides with measurements obtained using a new ELISA specific for dimeric inhibin-A. It was hypothesized that granulosa cell tumours may secrete significant quantities of inhibin-A whereas mucinous tumours were unlikely to do so because of the lack of a relation between INH and FSH measurements in the latter group. DESIGN: Serum samples obtained from women found to have ovarian cancer were assayed using the heterologous radioimmunoassay (the Monash assay) and using an ELISA specific for dimeric inhibin (the Groome assay) and the results were compared. PATIENTS: Samples for assay were available from 69 normal post-menopausal control women, 12 patients with mucinous tumours of the ovary, 26 with serous tumours, 7 with granulosa cell tumours and 8 with various other ovarian tumours. Patients were post-menopausal or had been subjected to bilateral oophorectomy at the time these samples were collected. MEASUREMENTS: The Monash and Groome assays were carried out as described previously. The upper limit of normal for post-menopausal women in the Monash assay was 122 U/l and for the Groome assay was calculated to be 32 ng/l. RESULTS: Among the 69 normal subjects, 4 were found to have elevated inhibin levels using the Monash RIA (133-190 U/l) and 4 were found to have elevated levels in the Groome ELISA (45.5-55.3 ng/l). Among 12 patients with mucinous tumours, 10 (83%) had elevated inhibin levels using the Monash assay but only 3 (25%) had elevated levels with the Groome assay (P < 0.005). Among 26 with serous tumours, 15 (58%) had elevated levels in the Monash assay but only 1 (4%) in the Groome assay (P < 0.001). Among 7 samples from patients with granulosa cell tumours, 100% were elevated in the Monash assay and 71% in the Groome assay (NS, non-significant). In a miscellaneous group of tumours all 8 had elevated levels in the Monash assay and 2 in the Groome assay (P < 0.001). CONCLUSIONS: It was concluded that in normal postmenopausal subjects, INH is generally undetectable or present at low levels, consistent with the loss of ovarian function. The majority of granulosa cell tumours appear to secrete significant amounts of dimeric inhibin-A, whereas mucinous tumours secrete predominantly other forms of INH, presumably related to the alpha-subunit. Serous tumours may also secrete inhibin-related peptides but not dimeric inhibin-A. The nature of the inhibin related peptides produced by epithelial ovarian cancers remains to be characterized.
Menorrhagia affects approximately 9% of all women, increasing to 20% during the perimenopause. The majority of menstrual loss occurs through the spiral arterioles - specialized endometrial vessels that are intimately involved in controlling menstruation. Our aim was to compare the distribution of vascular smooth muscle alpha-actin using immunohistochemical techniques in the endometrium of women before and during the perimenopause and with or without menorrhagia. We hypothesized that differences in vessel numbers and types exhibiting alpha-actin staining would exist between these groups, reflecting structural/functional differences. The results showed that perimenopausal menorrhagic women had significantly more smooth muscle alpha-actin expression than non-perimenopausal controls in four out of five menstrual cycle stages (P < 0.05), while perimenopausal non-menorrhagic women demonstrated a significant increase at the mid-proliferative stage only (P < 0.007). No significant differences occurred between women with or without menorrhagia before or during the perimenopause. Perimenopausal women had significantly more straight arterioles (P < 0.02) than women prior to perimenopause at the late secretory stage, while non-perimenopausal women demonstrated significantly higher numbers of spiral arterioles (P < 0.002) in the early secretory stage, although this difference had disappeared by the late secretory stage. In conclusion, we found no major differences in endometrial vascular smooth muscle alpha-actin staining between women with and without menorrhagia, but significant increases in alpha-actin staining in women showing perimenopausal symptoms.
Local endometrial aberrations are thought to be the major contributing factor to essential menorrhagia. Here we have examined the role of endometrial angiogenesis, the growth of new blood vessels, in essential menorrhagia. Our study tested two hypotheses: firstly that angiogenesis is disturbed in the endometrium of women with menorrhagia; and secondly that when menstrual blood loss is decreased following endometrial ablation, an endometrial environment favouring normal angiogenesis has returned. Angiogenesis was measured by endothelial cell proliferation. Proliferating endothelial cells were identified by an immunohistochemical double staining technique. A total of 57 women participated in this study, of whom 19 were controls, 20 had menorrhagia and 18 were 3-6 months post-ablation. There was a significant increase in endothelial cell proliferation in the endometrium of patients with menorrhagia compared with the control endometrium. Conversely, post-ablation endometrium showed a non-significant decrease in endothelial cell proliferation. The increased endothelial cell proliferation in the endometrium of patients with menorrhagia was not the result of a general increase in endometrial cellular proliferation and did not result in a change in endothelial cell concentration compared with control endometrium. These results support the hypothesis that angiogenesis is disturbed in the endometrium of patients with menorrhagia and normalized in post-ablation endometrium.
This study tested the hypothesis that alterations in the expression of oestrogen and progesterone receptors (ER and PR) in endometrial vascular smooth muscle cells (VSMC) may play a role in the increased blood loss that occurs during menorrhagia. Subject groups were: controls (n = 40), those with menorrhagia (menstrual blood loss > 80 ml, n = 39) and patients post-endometrial ablation (n = 16). The aims of our study were to describe the changing distribution of VSMC ER and PR during the menstrual cycle and to look for differences between the three groups. Immunohistochemical double-staining results for VSMC and either ER or PR were highly varied, with 0-85% of endometrial arterioles in a biopsy section having alpha smooth muscle actin/ER positive cells, and 0-70% demonstrating PR. There were no significant differences between controls, menorrhagia or post-ablation specimens (analysis of variance for ER P = 0.72; for PR P = 0.17). There were also no significant differences between the different stages of the menstrual cycle when all three groups were combined (analysis of variance for ER P = 0.11; for PR P = 0.13). The high variability found in this study may mask biologically relevant differences in endometrial vascular ER and PR distribution between different groups.
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Immunoreactive adrenocorticotropin (ACTH), beta-endorphin (BEP) and corticotropin-releasing factor (CRF) were detected in human term placenta obtained from elective Caesarian surgery. The concentrations of ACTH, BEP and CRF in placenta detected by radioimmunoassay (RIA) were 2.83 +/- 0.36, 0.52 +/- 0.05 and 0.56 +/- 0.15 ng/g wet weight of tissue respectively. Pro-opiomelanocortin (POMC) peptides were also detected in the amnion and chorion membranes and in the decidua. The concentrations of ACTH were 1.72 +/- 0.20, 4.43 +/- 0.39 and 5.80 +/- 0.17 ng/g and the levels of BEP were 0.42 +/- 0.18, 0.65 +/- 0.20 and 3.66 +/- 1.10 ng/g in the amnion, chorion and decidua respectively. In contrast to placenta, immunoreactive CRF was not detected in the amnion, chorion and decidua. Immunoreactive N-acetylated BEP was also not detected in all the placental subfractions. Comparison of the amounts of both ACTH and BEP in the various placental components indicated the following distribution: decidua > chorion > placenta > amnion. In decidua, POMC peptides were present in an equi-molar ratio but in the other three placental fractions, ACTH levels were three to five-fold higher than BEP. In immunohistochemical studies, only a positive staining for ACTH was obtained for decidua. Our results confirm the presence of POMC peptides and CRF in placenta and their physiological roles in pregnancy and parturition.
OBJECTIVE: To test the null hypothesis that asymmetric or incongruent follicular development does not influence GIFT pregnancy rates (PRs). DESIGN: A prospective comparative study. SETTING: Tertiary referral center for infertility. PATIENT(S): Ninety-three consecutive infertile patients having GIFT. INTERVENTION(S): Controlled ovarian hyperstimulation and GIFT. MAIN OUTCOME MEASURE(S): The incongruity ratio as a parameter of the asymmetry in follicular development and the clinical PR. RESULT(S): An inverse relationship was observed between the degree of incongruity and the clinical PRs. In patients with an incongruity ratio < 1.5, the clinical PR was 56.1%. In patients with an incongruity ratio > or = 1.5, the clinical PR was only 17.3%. CONCLUSION(S): Incongruent follicular development during controlled ovarian hyperstimulation has a marked negative influence on the outcome of GIFT cycles. Factors such as side of the gamete transfer and oocyte quality did not account for the observed differences.
Elevated serum immunoreactive inhibin concentrations have been reported in patients with mucinous and granulosa cell tumors of the ovary. The present study aimed to determine whether the inhibins and/or the related peptides, the activins, were demonstrable within ovarian tumor tissue. Immunohistochemical analyses were performed on 11 ovarian tumors, 5 mucinous, 3 serous, 1 granulosa, 1 clear cell, and 1 metastatic colonic cancer. Both monoclonal and polyclonal antisera specific for inhibin-A, activin-A, and activin-B, and their alpha-, beta A- and beta B-subunits were used. The mucinous cells of all five mucinous tumors showed positive staining for activin-A and activin-B, and their beta A- and beta B-subunits, and three stained positive for inhibin-A and the alpha-subunit. The granulosa cell tumor also showed positive staining for inhibin-A and the activins. The remaining tumors were negative. The findings are consistent with the hypersecretion of inhibin (and possibly activin) by some ovarian malignancies and suggest that immunohistochemistry for the inhibins and the activins should be explored further in the classification of ovarian malignancies.
OBJECTIVE: To compare the proliferation of endothelial, epithelial, and stromal cells in the endometrium of women with endometriosis and normal controls. DESIGN: Proliferating cells were identified using the monoclonal antibody antiproliferating cell nuclear antigen. A second antibody (CD34) was used to identify endothelial cells (ECs). SETTING: University Department of Obstetrics and Gynaecology. PATIENTS: Women with laparoscopically proven endometriosis, n = 30. Controls were women with a normal pelvis at laparoscopy performed for tubal sterilization or for infertility due to a male factor, n = 27. MAIN OUTCOME MEASURES: Endothelial cells: proliferative index. Epithelial and stromal cells: semi-quantitative immunostaining score. RESULTS: The mean EC proliferative index was significantly greater in those with endometriosis compared with controls. This difference was most marked during the proliferative phase of the menstrual cycle. Proliferative phase epithelial and stromal cells demonstrated significantly higher immunostaining scores in endometriosis patients than in controls. CONCLUSIONS: We have demonstrated increased numbers of proliferating ECs as well as epithelial and stromal cells in proliferative phase endometrium of women with endometriosis. This suggests that the endometrium of these women might have an enhanced ability to implant and survive in ectopic locations.
Inhibin was first isolated in 1985. Major progress has been made in defining various aspects of its structure and physiology, using a heterologous radioimmunoassay. Current research is aimed at characterizing the nature of the circulating forms of inhibin and is examining whether there are sex-specific roles for inhibins A and B. It has been recognized that various forms of epithelial and stromal ovarian cancer produce members of the inhibin peptide family but the precise nature of these products is not yet clear. The recognition that the inhibin subunits together with follistatin are expressed locally within the pituitary has lead to an investigation of their possible roles in intrapituitary regulation. It is clear that these peptides also have intragonadal roles. Of particular current interest is the nature of the signals that control the specificity of cellular peptide production and that determine whether a particular cell produces inhibin or activin. The inhibins are members of a complex family with many potential roles in physiology and pathophysiology. The role of the inhibins in feedback control of follicle stimulating hormone in the male, particularly, remains unclear. New applications for inhibin and related peptides are likely to be developed.
While no single biochemical test is diagnostic of polycystic ovary syndrome (PCOS), most patients show a characteristic ovarian ultrasonographic appearance. It has been proposed that a dysfunction of cytochrome P-450c17 alpha in PCOS leads to an increased 17-hydroxyprogesterone (17-OHP) response to a gonadotrophin-releasing hormone (GnRH) agonist-induced gonadotrophin rise. We postulated that this abnormality of steroid metabolism might influence the ovarian response during assisted reproduction treatment. We investigated 106 patients undergoing a short 'boost' stimulation regimen for assisted reproduction treatment, including in-vitro fertilization and gamete intra-Fallopian transfers. The ovarian ultrasound pattern was correlated with serum testosterone, 17-OHP, androstenedione and oestradiol responses, and with the clinical outcome. Polycystic ovaries, defined ultrasonographically as the presence of > or = 10 follicles between 2 and 10 mm diameter in either ovary, were found in 48% of the whole study population. Dexamethasone was given to suppress adrenal androgen secretion. Functional ovarian hyperandrogenism (FOH) was defined as serum testosterone > 0.5 nmol/l after dexamethasone. There was a significantly (P < 0.001) higher prevalence of FOH in patients with polycystic ovaries (23%) compared with normal ovaries (7%). Patients with polycystic ovaries had approximately double the 17-OHP, androstenedione and oestradiol responses to a GnRH agonist as patients with non-polycystic ovaries. Exaggerated 17-OHP and oestradiol responses to GnRH agonist were found in 89% of patients with clinically diagnosed PCOS. The number of oocytes retrieved was positively correlated (r = 0.51, P < 0.001) with the oestradiol responses in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Fibroids (leiomyomata) are the commonest tumours in women, but their aetiology is unknown. Epidermal growth factor (EGF) and transforming growth factor-beta (TGF beta) may be important factors involved in fibroid growth. We examined the mRNA expression of these two growth factors in fibroids and corresponding myometrium from 20 women who underwent hysterectomy because of fibroids. We also examined these factors in samples of fibroids from 9 women who underwent myomectomy after pretreatment with luteinizing hormone-releasing hormone agonists. We found that both factors were expressed in the three types of tissue examined. We also found that there was no difference in the relative abundance of either of the two growth factors between the tissues studied. Despite the lack of difference, we postulate that EGF and TGF beta may be important in fibroid growth because of a possible interaction between the two factors in this tissue.
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