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Biomedical subjects

D L Healy

Publications and source records attributed to D L Healy.

At least 55 records · Page 3Linked to original sources
PubMed1994

Vascular endothelial growth factor as capillary permeability agent in ovarian hyperstimulation syndrome.

We investigated the role of vascular endothelial growth factor (VEGF) in ovarian hyperstimulation syndrome (OHSS). Two similar peaks of permeability activity were seen in OHSS ascites and liver ascites spiked with recombinant human VEGF (rhVEGF); no activity was seen in control liver ascites. Incubation with rhVEGF antiserum decreased activity in the two OHSS peaks by 79% and 65% and the two spiked liver peaks by 49% and 50%. Control serum produced 24% and 27%, and 17% and 0% reductions, respectively. This is evidence that the major capillary permeability agent in OHSS ascites fluid is VEGF.

Animals↗
PubMed1994

Endometrial ablation: an option for the management of menstrual problems in the intellectually disabled.

OBJECTIVE: To evaluate endometrial ablation as an alternative to hysterectomy for intellectually disabled women with inadequate menstrual hygiene. DESIGN AND SETTING: A retrospective review of all intellectually impaired women referred to a menstrual management clinic at a university teaching hospital for management of inadequate menstrual hygiene between October 1989 and September 1992. RESULTS: Endometrial resection was considered an appropriate alternative to hysterectomy for eight intellectually disabled women. To date, seven women have undergone the procedure and one is receiving medical treatment. Endometrial ablation was performed with roller-ball electrocautery. Three patients underwent sterilisation at the time of surgery. The mean operating theatre time was 75 minutes. Postoperative hospital stay was less than 48 hours for all but one patient, who underwent minilaparotomy for sterilisation--postoperative analgesia was required only by this patient. There were no complications during or after surgery. Six weeks after surgery, all patients were amenorrhoeic and they and/or their carers expressed satisfaction with the procedure. Four women, followed up for between 16 and 38 months, remain amenorrhoeic and two, followed up for six months, have each experienced one episode of spotting but are otherwise amenorrhoeic. The seventh patient has had irregular bleeding but this is deemed due to erroneous continuation of progesterone therapy and is being monitored. CONCLUSION: Endometrial ablation provides a valuable alternative to hysterectomy. It should be the surgical treatment of choice for intellectually disabled women with inadequate menstrual hygiene unresponsive to medical therapy.

Adolescent↗
PubMed1994

Gynaecological care for women with intellectual disability.

Optimal gynaecological care for women with intellectual disability is complex. Many of these women suffer unique problems with regard to menstrual hygiene, sexuality, contraception and susceptibility to sexual abuse. Complex medical, ethical, social and legal issues must be carefully considered to address these problems. We discuss the "gynaecological" management of intellectually disabled women, with particular reference to contraception and menstrual suppression. We advocate endometrial ablation as an alternative to hysterectomy for women with intractable menstrual problems. Some ethical issues are reviewed which must be addressed to determine which approach is in the patient's "best interest" and adopts the "least restrictive option". Finally, we present Federal and State laws governing informed consent for medical procedures for women and children with intellectual disabilities.

Adult↗
PubMed1994

A prospective study of inhibin in granulosa cell tumors of the ovary.

Elevated preoperative serum inhibin concentrations have been reported in patients with granulosa cell tumor of the ovary. The aim of this study was to determine if elevations in serum inhibin predated clinical recurrence in patients with a diagnosis of granulosa cell tumor. Twenty-seven consecutive patients with granulosa cell tumor were followed prospectively to assess the relationship between serum inhibin concentrations and disease status. The serum inhibin concentrations in normal postmenopausal women were < 77-130 U/liter. In patients with granulosa cell tumor at initial surgery, mean inhibin concentrations preoperatively were 2831 U/liter in 4 postmenopausal subjects (range 2130-3323 U/liter) and 3680 U/liter in each of 2 premenopausal women. In 5 postmenopausal subjects with a histological diagnosis of granulosa cell tumor who underwent secondary surgery because of a recurrent palpable mass, mean inhibin concentrations were 4216 U/liter (range 2672-7360). In 3 patients with known or suspected residual disease despite a secondary debulking operation the serum inhibin concentrations were 475, 1000, and 2541 U/liter. In 13 subjects who were clinically disease free with a previous diagnosis of granulosa cell tumor, serum inhibin concentrations remained within the normal range for reproductive status. We conclude: (1) Preoperative serum inhibin concentrations are typically elevated sevenfold above the normal premenopausal follicular phase levels in women with granulosa cell tumor; (2) after surgery, serum inhibin levels may become elevated up to 2 years before further surgery is undertaken; and (3) serum inhibin concentrations appear to be a valuable tumor marker for the diagnosis of primary or recurrent granulosa cell tumor.

Adult↗
PubMed1994

Image analysis quantification of the Miles assay.

The Miles assay for vascular permeability has high intra- and interassay coefficients of variation (CVs). Quantification, usually by dye extraction and spectrophotometry, is time consuming. In this study, quantification by this means was compared with image analysis using the Olympus CUE-2 Image Analyzer (version 4). The test substance was recombinant human vascular permeability factor (rhVPF). The quantification process took approximately 10 min with image analysis. Formamide extraction and spectrophotometry required 1 hr of preparation, 4-6 days of incubation, and 1 hr for filtration and spectrophotometry. Between assay CVs ranged from 0 to 30% for spectrophotometry, but were all < 10% for image analysis. The sensitivity (2SD above the negative control mean) of the image analysis approach was 64 +/- 25 ng/mL, whereas for spectrophotometry it was 65 +/- 29 ng/mL. Interanimal CVs for rhVPF at 200 and 1000 ng/mL were 15% and 26% when assessed by spectrophotometry and 7% and 22%, respectively, by image analysis. The R2 value for the correlation of image analysis with spectrophotometry was 81.4%. Test substances injected close to the spine evoked a greater permeability response than those injected laterally: at 200 ng/mL p = 0.005, at 1000 ng/mL p = 0.1 (unpaired t tests).

Animals↗
PubMed1994

Messenger RNA encoding the insulin-like growth factors and their binding proteins, in women with fibroids, pretreated with luteinizing hormone-releasing hormone agonists.

The primary objective of this study was to suggest a possible mechanism of action of luteinizing hormone-releasing hormone agonist (LHRHa) on fibroids. This was performed by investigating insulin-like growth factor (IGF)-I, IGF-II and IGF binding protein (IGFBP)-1, -2 and -3 mRNA expression in uterine fibroids from women rendered hypo-oestrogenic by LHRHa, using Northern blot analysis. Nine women with fibroids, who were rendered hypo-oestrogenic from at least 4 months pretreatment with LHRHa therapy prior to undergoing myomectomy were investigated. Our results showed that IGF-I, IGF-II, IGFBP-2 and -3 mRNAs were expressed in uterine fibroids, and that IGFBP-1 mRNA or protein was not detected in fibroids. Western ligand blotting showed the presence of IGFBP-2 and -3 proteins, and when compared with a group of women with fibroids not treated with LHRHa (B.J. Vollenhoven et al., 1993, J. Clin. Endocrinol. Metab., 76, 1106-1110) we found that there was no difference in the relative abundance for each of the factors between the two groups of women. Therefore, LHRHa act to decrease fibroid size via induction of a hypo-oestrogenic state rather than by changes in the IGFs and their IGFBPs.

Adult↗
PubMed1994

Human follicular fluid maturity and endothelial cell chemotaxis.

Follicular fluid of varying maturity was collected from the largest Graafian follicle of 23 ovulatory patients during laparoscopy (five blood-stained samples were discarded) and from five patients undergoing oocyte collection for assisted reproduction. The endothelial cell (EC) chemotactic potentials of the samples were tested with bovine aortic ECs in modified Boyden Chambers and an EC density score was determined for each sample. Intra-assay coefficients of variation (CV) varied from 2.9-17%; inter-assay CV was 45%. Therefore, cell density scores were expressed in terms of positive and negative control values from their respective plates. Serum progesterone was positively correlated with EC chemotactic potential (R2 = 14.9%). There was no correlation with day of cycle, follicular diameter, serum luteinizing hormone (LH) or oestradiol, or follicular fluid total protein levels (all R2 < or = 6%). Five subjects were in early and four in mid-follicular phase, seven were in early and two in late LH surge, and there were also five in-vitro fertilization (IVF) specimens. There was a statistically significant difference between the EC chemotactic potential of the five groups by analysis of variance (F = 5.98; P = 0.006). There was no significant difference between the late LH surge and the IVF samples (two-sample t-test). The mean cell density was higher for these two groups than the other three (P < 0.01 in all cases; two-sample t-test). It is concluded that the EC chemotactic potential of human follicular fluid increases after the LH surge and before ovulation.

Adult↗
PubMed1994

An immunohistochemical study of the vascularization of the human Graafian follicle.

The wall of the largest Graafian follicle or corpus luteum was biopsied in 22 patients at laparoscopy. Both granulosa and theca cells were contained in 18 samples. These samples were classified as pre-luteinizing hormone (LH) surge (n = 3), LH surge (n = 3), early luteal (n = 3), mid-luteal (n = 4), late luteal (n = 3) and menstrual (n = 2). A double-staining immunohistochemical protocol was used to demonstrate proliferating endothelial cells: mouse-anti-rat-proliferating cell nuclear antigen, for proliferating cells; mouse-anti-human-CD34 antibody for endothelial cells. The percentage of endothelial cells proliferating (proliferation index) and the area of tissue occupied by endothelial cells (areal fraction) were determined for granulosa and theca layers. Intra- and inter-slide coefficients of variation were < 15%. The granulosa layer was avascular until the LH surge subsided. Maximum vascularization was achieved by the mid-luteal phase. The theca endothelial cell proliferation index was constant from pre-LH surge to mid-luteal phases. The mean theca endothelial cell proliferation index for these phases was significantly greater than for the late luteal and menstrual phases. From first appearance in the granulosa layer, endothelial cells had the same proliferation index as the theca endothelial cells, the proliferation index decreasing significantly in both after the mid-luteal phase (P = 0.018). It is concluded that endothelial cell proliferation is unchanged throughout the follicular, early and mid-luteal phases, decreasing significantly in the late luteal phase. By contrast, endothelial cell invasion of the membrane granulosa, presumably in response to a chemotactic stimulus, occurs after the LH surge has subsided.

Antigens, CD↗
PubMed1994

Steroid receptor binding and messenger RNA expression in fibroids from untreated and gonadotrophin-releasing hormone agonist pretreated women.

OBJECTIVE: The hypothesis of this study was that oestrogen may play a role in fibroid growth and that a lack of oestrogen may be the reason for gonadotrophin-releasing hormone agonist (GnRHa) induced fibroid shrinkage. Therefore our aims were (1) to investigate oestrogen receptor (ER) and progesterone receptor (PR) binding in fibroids and myometrium from untreated women and in fibroids from GnRHa pretreated women, (2) to evaluate the mRNA expression of ER and PR in these tissues, and (3) to examine whether a correlation existed between receptor binding and mRNA expression for ER and PR. DESIGN: Cytosolic ER and PR binding was assessed by the dextran-coated charcoal technique and ER and PR mRNA expression was assessed using Northern blots of total RNA. PATIENTS: Fibroid and corresponding myometrial specimens were obtained from 20 women undergoing hysterectomy while fibroid specimens only were obtained from 10 women undergoing myomectomy after at least 3 months pretreatment with GnRHa. RESULTS: We found that (1) ER binding was twice and PR binding was three times as great in fibroid as in myometrium and that there was no difference in binding for either receptor between fibroids from untreated and GnRHa pretreated women, (2) ER and PR mRNA abundances were similar in fibroids and myometrium from untreated women and in fibroids from untreated and GnRHa pretreated women, and (3) ER binding and ER mRNA abundance in both groups of fibroids and myometrium were independent of each other, but there was a positive correlation between PR binding and PR mRNA abundance in untreated fibroids and myometrium but not in GnRHa pretreated tumours. CONCLUSIONS: We conclude that (1) both oestrogen and progesterone may contribute to fibroid growth because of increased receptor binding in fibroids compared with myometrium and (2) in GnRHa treated women, fibroids may shrink because of a lowered circulating oestradiol level rather than because of a change in steroid receptor binding.

Adult↗
PubMed1994

Endometrial sex steroid receptor expression in women with menorrhagia.

OBJECTIVE: To investigate the oestrogen and progesterone receptor distribution in endometrium from reproductive age and perimenopausal women with and without menorrhagia. DESIGN: A comparative observational study. SUBJECTS: Forty-five women with objective menorrhagia (27 categorised as reproductive age and 18 as perimenopausal) and a control group of 44 women (31 reproductive age and 13 perimenopausal) with menstrual blood loss of less than 80 ml per period. MAIN OUTCOME MEASURES: Oestrogen receptor and progesterone receptor semi-quantitative immunostaining scores. RESULTS: Comparison of control and menorrhagic endometrium in this study (whether from reproductive age or perimenopausal subjects) failed to demonstrate any major differences in either sex steroid receptor mean immunostaining score. The results demonstrated a great degree of variability in sex steroid receptor immunoreactivity between individuals. Irrespective of clinical group, significant increases in immunostaining were demonstrated in the proliferative phase of the cycle for immunoreactivity of oestrogen receptor in glands (P < 0.0005), and stromal (P = 0.002) compartments of endometrium and progesterone receptor immunoreactivity in glands (P = 0.009). Progesterone receptor immunostaining in the stromal compartments did not significantly decline (P = 0.06) in the secretory phase. CONCLUSIONS: Endometrium from women with objective evidence of menorrhagia is indistinguishable in terms of sex steroid immunoreactivity from endometrium of women with normal monthly blood loss. This pattern of sex steroid receptor immunostaining pattern was maintained into the perimenopausal years.

Adult↗
PubMed1994

Prostaglandins and progesterone receptor antagonists in human fertility regulation.

Anti-progesterone medicines have now been extensively studied for human fertility regulation. The combination of the anti-progesterone Mifepristone with prostaglandin analogues such as Gemeprost and Misoprostol have been used in several European centres for medical abortion. Used before nine weeks gestation, these medicines have similar efficacy to surgical abortion. In addition, administration of progesterone antagonists within five days of unprotected intercourse appear effective in pregnancy prevention. Anti-progesterone medicines are not currently available in Australia. The introduction of progesterone receptor antagonists and modern prostaglandins would save approximately $10,000,000 per year to the Australian Health Budget. Furthermore, the introduction of progesterone receptor antagonists for emergency contraception would have even greater financial and emotional savings for Australian women. In Australia, when known carcinogens can be purchased over the counter, it is surely time for Australians to consider effective emergency contraception bought over the counter.

Abortion, Induced↗
PubMed1994

Is ovarian relaxin a stimulus to placental protein 14 secretion in pregnancy?

The objective of this study was to investigate whether relaxin might be involved in placental protein 14 (PP14) secretion by measuring serum levels of PP14 during labour and post partum in normal women with a term pregnancy given vaginal human recombinant relaxin (rhRlx) gel for induction of labour. A randomized double-blind controlled trial was conducted on 11 women with a singleton pregnancy at term admitted for induction of labour. Comparison of serum PP14 and relaxin concentrations in the control and treated groups of subjects revealed that there was an increase in serum relaxin concentrations in women receiving 3 mg or 6 mg relaxin. There was no difference in serum PP14 levels between the control and treatment groups. These findings do not support the hypothesis that relaxin is involved in the control of PP14 secretion. However, the failure of any response might be a consequence of the very small increase in systemic levels of relaxin produced by topical vaginal administration of rhRlx. Furthermore, these measurements were made in late pregnancy and hence may not relate to the events in early pregnancy, when serum levels of PP14 are maximal.

Adult↗
PubMed1993

Elevated serum inhibin concentrations in postmenopausal women with ovarian tumors.

BACKGROUND: Inhibin is an ovarian hormone that inhibits the secretion of follicle-stimulating hormone (FSH) by the anterior pituitary gland. Women with granulosa-cell tumors of the ovary have elevated serum inhibin concentrations, but whether the concentrations are increased in women with other ovarian tumors is unknown. METHODS: We measured serum inhibin and FSH concentrations before surgery in 212 postmenopausal women with suspected ovarian cancer and after surgery in 210 of them. RESULTS: Eighteen of the 22 women (82 percent) with mucinous carcinomas (mucinous cystadenocarcinomas and mucinous borderline cystic tumors) of the ovary had elevated serum inhibin concentrations, whereas only 9 of the 53 women (17 percent) with serous carcinomas (serous cystadenocarcinomas and serous borderline cystic tumors) had elevated levels. Serum inhibin concentrations were also elevated in 2 of 12 women (17 percent) with clear-cell carcinomas, 4 of 26 women (15 percent) with undifferentiated carcinomas, 3 of 3 women (100 percent) with granulosa-cell tumors, and 5 of 27 women (19 percent) with other ovarian cancers. The serum concentrations of inhibin were increased in 2 of 28 women (7 percent) with nonovarian pelvic cancers and 11 of 41 women (27 percent) with benign ovarian diseases. All women but one with initially elevated serum inhibin concentrations had low values one week after surgery. Serum inhibin concentrations correlated negatively with serum FSH concentrations (P = 0.05) in women with granulosa-cell tumors but not in women with other tumors, suggesting that the inhibin secreted by tumors in the latter group has decreased biologic activity. CONCLUSIONS: Serum inhibin concentrations are elevated in most postmenopausal women with mucinous carcinomas of the ovary and in some women with other types of epithelial ovarian tumors. The concentrations fall after tumor removal.

Adenocarcinoma, Clear Cell↗
PubMed1993

Age and follicular phase estradiol are better predictors of pregnancy outcome than luteinizing hormone in menotropin ovulation induction for anovulatory polycystic ovarian syndrome.

OBJECTIVE: To examine the relationship of baseline and preovulatory serum E2, P, and LH levels and age with pregnancy outcome in polycystic ovarian syndrome (PCOS) patients undergoing hMG ovulation induction. DESIGN: Retrospective analysis of all available data over 2 years. SETTING: Tertiary referral ovulation induction clinic. SUBJECTS: Forty-four anovulatory PCOS patients with 25 ovulatory nonconception and 50 conception cycles after hMG ovulation induction. MAIN OUTCOME MEASURES: Ovulation (midluteal serum P > 25 nmol/L [7.86 ng/mL]); pregnancy (serum beta-hCG > 30 mIU/mL 16 days after ovulating injection); pregnancy outcome: pregnancy termination < 20 weeks' or > or = 20 weeks' amenorrhea. RESULTS: Of the endocrine parameters considered, none was significantly different in nonconceptive and conceptive ovulatory cycles. Miscarriage was associated with low basal serum E2: median value for pregnancies ending < 20 weeks, 105 pmol/L (28.6 pg/mL) and for > or = 20 weeks 150 pmol/L (40.9 pg/mL). It was also significantly associated with age. For patients > 29.5 years of age, (29.5 years, population mean age) a baseline E2 < or = 140 pmol/L (38.2 pg/mL) had sensitivity 92%, specificity 54%, positive predictive value 65%, and negative predictive value 87% for the prediction of miscarriage. The nature of the previous cycle, the day of the cycle on which therapy commenced, and a past history of miscarriage were not related either to pregnancy outcome or to basal serum E2.

Abortion, Spontaneous↗
PubMed1993

Serum immunoactive inhibin levels in early pregnancy after in vitro fertilization and embryo transfer.

OBJECTIVE: To determine the maternal serum concentrations of inhibin, E2, P, and hCG in early pregnancies arising from IVF and ET or GIFT and to assess the value of these hormone measurements in determining outcome of pregnancy. DESIGN: Serum immunoactive inhibin, E2, P, and hCG levels were measured in the first trimester of pregnancies after IVF-ET and GIFT procedures. SETTING: In vitro fertilization and ET or GIFT was undertaken at Monash IVF, Melbourne, Victoria, Australia. PATIENTS: At least two blood samples were collected from 117 women between 4 and 11 weeks of gestation. MAIN OUTCOME MEASURES: The hormone concentrations in the IVF-ET and GIFT pregnancies were compared with those in pregnancies and related to outcome of pregnancy. RESULTS: Serum inhibin levels in singleton pregnancies were significantly higher than in comparable normal pregnancies. In contrast to normal conceptions in which inhibin concentrations rose to peak at 11 weeks, the levels found in IVF-ET and GIFT singleton pregnancies were high at 5 weeks' gestation and declined subsequently. In twin pregnancies, the inhibin levels were significantly greater than those in singleton pregnancies. In biochemical pregnancies diagnosed by increasing hCG concentrations in the absence of an embryonic sac, inhibin levels were significantly lower than those found in singleton pregnancy, as were E2, P, and hCG levels. In anembryonic pregnancies, diagnosed by the confirmation of an intrauterine gestation sac with no evidence of a fetal complex, inhibin concentrations were highest at week 4 and declined, being significantly lower at all stages of gestation. In ectopic pregnancy, serum inhibin levels were lower at all stages of gestation, whereas E2 concentrations were not lower until 6 weeks and P levels until week 5. Serum hCG levels were significantly lower at all stages of gestation. In women with spontaneous abortions, inhibin levels were lower than singleton pregnancies at 7 weeks. CONCLUSIONS: Serum inhibin concentrations are elevated in pregnancies arising from ovarian hyperstimulation in the first trimester when compared with those in normal pregnancy, probably as a result of the presence of multiple corpora lutea resulting from ovarian hyperstimulation. Serum inhibin, E2, P, and hCG are useful markers of abnormal pregnancy outcome.

Chorionic Gonadotropin↗