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Biomedical subjects

D L Healy

Publications and source records attributed to D L Healy.

At least 73 records · Page 4Linked to original sources
PubMed1993

Endometriosis: medical therapy.

The management of women with endometriosis is complex and necessitates individualization of patient care. The most commonly used medical therapies are danazol, GnRH agonists, medroxyprogesterone acetate and gestrinone. Studies to date have shown these drugs to have equal efficacy in terms of reduction in laparoscopic score and relief of symptoms. However, their side-effects make them unsuitable for long-term use. The addition of low dose hormone replacement therapy to GnRH agonist regimens may allow prolonged use but the current cost of these agents is high. Low dose oral contraceptive pills deserve further investigation. The role of medical treatment for women with endometriosis and infertility is controversial. There is no place for hormonal therapy in such women with stage I or II disease. When expectant management fails, gamete intrafallopian transfer offers excellent results. For those with stage III or IV disease, surgery is preferable with adjunctive medical therapy in selected cases. If pregnancy does not ensue, in vitro fertilization and embryo transfer are the next line of management, and results are optimized by prior medical therapy and aspiration of endometriomas. Major advances have been made in the medical management of endometriosis. However, current treatment strategies are ineffective in eliminating the disease in most women. New approaches are required in both basic and clinical research in order to finally eradicate this often devastating disease.

Danazol↗
PubMed1993

Clinical and pathophysiological aspects of inhibin.

Inhibin is a peptide hormone normally produced by the ovary. We have previously reported that serum inhibin concentrations are elevated in patients with granulosa cell tumours of the ovary. The aim of this study was to measure serum inhibin in a prospective, consecutive series of 200 patients admitted for suspected ovarian cancer. The serum inhibin radioimmunoassay had a sensitivity of 77 mu/l. The median effective dose was 640 mu/l, while within- and between-assay coefficients of variation in the region of maximal assay precision were 4.3% and 4.3%, respectively. The average effective doses (10 and 90%) in 35 consecutive assays were 211 and 1908 mu/l, respectively. We designated a serum inhibin concentration of > or = 130 mu/l as pathological in castrate or functionally agonadal women. Serum inhibin concentrations were elevated in 12 of 13 post-menopausal patients with mucinous cystadenocarcinoma of the ovary. By contrast, elevated serum inhibin values were found in only nine of 65 women with non-mucinous epithelial ovarian cancers. All patients showed a fall in serum inhibin levels to below 130 mu/l by 1 week after surgery. In post-menopausal women (n = 54) with proven ovarian cancer, serum inhibin concentrations correlated negatively with serum FSH and the clinical stage of their disease (P < 0.05). By contrast, serum inhibin correlated positively with serum oestradiol and progesterone (P < 0.001) but there was no correlation between serum inhibition and serum CA-125 values. We conclude that serum inhibin concentrations are typically elevated in patients proven to have mucinous cystadenocarcinoma of the ovary.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1993

Human follicular fluid maturity and endothelial cell mitogenesis.

Follicular fluid, of varying maturity, (day 5-16 of cycle) was collected from the largest Graafian follicle of each of 22 ovulatory patients during laparoscopic procedures. Three samples were blood-stained and discarded. The mitogenic potential of each sample was determined using bovine aortic endothelial cells in the CellTiter 96 Non-Radioactive Cell Proliferation/Cytotoxicity Assay system. Intra- and inter-plate coefficients of variation were < 9%. The follicular fluid samples induced cell doubling times which varied from approximately 12-24 h and final cell numbers which, in the individual wells, ranged from 7828-30,900 (starting number 2000/well). Follicular fluid total protein content was unrelated to the mitogenic potential, (R2 = 0%). Serum oestradiol was negatively correlated with the mitogenic potential (R2 = 26%). No correlation was found with day of the menstrual cycle (R2 = 4.3%), maximum follicular diameter (R2 = 1.8%), or serum concentration of progesterone (R2 = 0.7%), luteinizing hormone (LH) (R2 = 1.5%) or follicle stimulating hormone (R2 = 0.1%). Five subjects were in 'early' and six in 'mid'-follicular phase, six were in 'early' and two in 'late' LH surge. There was no difference in the mitogenic response between these four groups by one-way analysis of variance (F = 0.21; P = 0.89). It is concluded that the mitogenic potential of human follicular fluid is not related to Graafian follicle maturity or, more particularly, to the LH surge.

Animals↗
PubMed1993

Messenger ribonucleic acid expression of the insulin-like growth factors and their binding proteins in uterine fibroids and myometrium.

Fibroids (leiomyomata) are the most common tumors in women, but their etiology is unknown. The insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) may be important in the growth of these benign neoplasms. We have examined the presence of mRNA encoding both IGF-I and IGF-II and IGFBP-1, -2, and -3 in fibroids and corresponding myometrium from 20 women undergoing hysterectomy for symptomatic uterine fibroids. Northern blots of total cellular RNA were probed with oligonucleotides for IGF-I, IGF-II, IGFBP-2, and IGFBP-3 and a human IGFBP-1 cDNA. Western ligand blotting was also used to detect the presence of IGFBP proteins in both fibroid and myometrium. The data showed that in fibroids compared to myometrium, 1) the relative abundance of IGF-I mRNA was not different, but there was an increase in the relative abundance of IGF-II mRNA (P < 0.001); 2) IGFBP-1 mRNA was undetectable in fibroids and detectable in only 1 specimen of myometrium; 3) there was no difference in the relative abundance of IGFBP-2 mRNA, but there was an increase in the relative abundance of IGFBP-3 mRNA in myometrium (P < 0.05). By Western ligand blotting, both IGFBP-2 and -3 proteins were present. Our data show that the mRNAs encoding IGF-I, IGF-II, IGFBP-2, and IGFBP-3 are expressed in both fibroids and myometrium and that fibroids express more IGF-II and less IGFBP-3 mRNA than myometrium. We postulate that the net effect of the changes seen is to increase the bioavailability of free (bioactive) IGF, which may then play a major role in promoting fibroid tumor growth.

Autoradiography↗
PubMed1993

Follicle-stimulating hormone induces dose-dependant stimulation of immunoreactive inhibin secretion during the follicular phase of the human menstrual cycle.

To determine whether FSH is a physiological regulator of the serum immunoreactive inhibin (INH) concentration during the follicular phase of the normal menstrual cycle, purified FSH (Metrodin) was administered in doses of 100 IU (n = 6), 150 IU (n = 5), and 200 IU (n = 5) to normal, regularly cycling volunteers between days 3-7 of the menstrual cycle. A control group (n = 5) received normal saline. There was a linear dose-related increase in serum INH (and in serum FSH) in response to the three doses of FSH, with 200 IU leading to a 107% increase in INH and a 68% increase in FSH. Serum estradiol rose in response to the two higher doses of FSH. There was a significant correlation between the actual increases in INH and estradiol (r = 0.53; P < 0.01). It was concluded that FSH stimulates INH in the follicular phase of the normal menstrual cycle, consistent with a physiological role for FSH in the regulation of granulosa cell production of inhibin.

Adult↗
PubMed1993

Is the luteo-placental shift a myth? Analysis of low progesterone levels in successful art pregnancies.

Progesterone (P4) is considered vital to the maintenance of human pregnancy, but the minimal concentration of P4 necessary to sustain human pregnancy remains unclear. The aim of this study was to examine endocrine profiles for serum P4, 17 beta-estradiol (E2), and human (h) beta-CG in early pregnancy from a group of assisted reproductive technologies (ART) patients. These subjects delivered normally but had P4 concentrations below the fifth percentile of the normal singleton pregnancy range from 2 weeks after ART. Normal ranges of these hormones were determined from 118 consecutive ART pregnancies which resulted in singleton births. Values below the fifth percentile (P4 < 35.9 nmol/L at 4 weeks gestation) were considered abnormal. Eight patients who subsequently delivered normally, with serum P4 values below this criterion at 4 weeks gestation, were found. They had serum P4 values at 4 weeks gestation ranging from 1.9-29.9 nmol/L, and their mean P4 values at 5 weeks (30.2 +/- 9.2 nmol/L; mean +/- SE) and 6 weeks gestation (48.0 +/- 10.2 nmol/L) remained below the fifth percentile. No statistically significant increase in serum P4 concentrations occurred between 7 and 11 weeks gestation in these women. Their mean E2 value in serum at 4 weeks gestation (382 +/- 73 pmol/L) was also below the fifth percentile but their mean beta-hCG concentration was within the normal range. We conclude that successful human pregnancy is possible with serum P4 values within the anovulatory range in early gestation and that, in individual patients, serum P4 concentration of 2 nmol/L can be sufficient to maintain human pregnancy.

Adult↗
PubMed1993

An open study of luteinizing hormone releasing hormone agonists in infertile women with uterine fibroids.

Twenty infertile women with fibroids were treated with luteinizing hormone releasing hormone agonists (LHRHa) to investigate if the use of these drugs, both with and without myomectomy, was effective in contributing to pregnancy in these women. All women had fibroids as their sole cause for infertility. Seven women conceived within 1 year of myomectomy or LHRHa treatment alone without myomectomy. The overall pregnancy rate was 36% and the postmyomectomy pregnancy rate was 50%. Initial fibroid size and extent of fibroid shrinkage on LHRHa therapy made no difference to the subsequent pregnancy rate. We also found no significant interaction between the number of fibroids present and the effect of myomectomy on the proportion of pregnancies. We conclude that the fertility enhancing value of myomectomy in otherwise idiopathic infertility is confirmed, and that the use of LHRHa premyomectomy in infertile women needs to be investigated in randomized controlled trials to assess its value as a preoperative therapy.

Adult↗
PubMed1993

Does gonadotropin suppression result in follicular development in premature ovarian failure?

It was hypothesized that premature ovarian failure is a self-perpetuating problem and that suppression of the endogenously raised gonadotropin levels may allow synchronization of follicular growth, so that when the suppression is removed, follicular development may be stimulated by the rapid rise in follicle stimulating hormone (FSH) levels. Microgynon (ethinylestradiol, 30 micrograms and levonorgestrel, 150 micrograms) was administered to eight women with premature ovarian failure for 12 weeks. Serum samples were collected weekly for radioimmunoassay of FSH, luteinizing hormone (LH), estradiol, progesterone and inhibin. On stopping Microgynon, ovarian ultrasonography was carried out, in addition to blood sampling, to monitor any follicular growth. Both FSH and LH levels declined to the normal follicular-phase range after 5 weeks of Microgynon treatment (mean +/- SD: FSH, 6.5 +/- 1.2 IU/l; LH, 8.9 +/- 1.6 IU/l). Both hormone levels rose rapidly after stopping treatment and were above the normal follicular-phase range by the 1st week. FSH reached pretreatment levels by 3 weeks, but LH did not reach the previously high levels until 7 weeks after stopping Microgynon administration. Estradiol and immunoreactive inhibin levels in serum were undetectable throughout the study. No follicular growth was seen on ultrasound scanning. Therefore, gonadotropin suppression in premature ovarian failure does not result in a resumption of follicular activity.

Adult↗
PubMed1992

Body weight, body mass index, and age: predictors of menotropin dose and cycle outcome in polycystic ovarian syndrome?

Whereas the dose of hMG is significantly correlated with both BMI and BW, commencing the more obese patient on higher hMG doses is not justified in view of the cancellation of cycles from over-responsiveness in the more obese patients started on higher hMG dosage regimens. If the more obese patient is slow to respond, however, a greater degree of clinical freedom may be exercised to increase the dose. The ultimate outcome of the cycle is not related to BMI, BW, or the dose of hMG used.

Aging↗
PubMed1992

Vaginal progesterone administration in physiological doses normalizes raised luteinizing hormone levels in patients with polycystic ovarian syndrome.

A raised luteinizing hormone (LH) level is a typical finding in the polycystic ovarian syndrome (PCOS). This inappropriate elevation of LH is thought to interfere with normal follicular development and ovulation. The resulting chronic anovulation is associated with the absence of the luteal phase increase in secretion of progesterone and inhibin. Progesterone can exert both a positive and negative feedback action on LH secretion, but inhibition is thought to occur following prolonged exposure to progesterone. Therefore, the aim of this study was to see if exogenously administered progesterone in physiological doses would normalize circulating LH concentrations in patients with PCOS. Vaginal progesterone was administered twice daily in a dose of 100 mg, at 12 h intervals, to ten women with PCOS. Serum samples were taken on alternate days for radioimmunoassay of follicle stimulating hormone (FSH), LH, estradiol, progesterone and inhibin. To determine the effect of progesterone on LH secretory dynamics in PCOS, LH pulse studies were carried out prior to treatment, and on day 10 of progesterone administration in four of the ten subjects. Mean serum progesterone concentrations reached 51 nmol/l by 4 days after exogenous progesterone treatment, and remained in the mid-luteal phase range, as established in 12 normal cycles, during the use of the vaginal suppository. The mean serum LH concentration had fallen significantly (p < or = 0.01) after 8 days of treatment, and continued to fall progressively until the end of progesterone administration. Serum LH concentrations had fallen into the normal follicular phase range by 14 days (mean 5.5, range 3.4-10.9 IU/l; normal follicular phase range 1.8-10.0 IU/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Estradiol↗
PubMed1991

Management of submucous uterine fibroid with buserelin, gemeprost and hysteroscopic resection.

A 19-year-old virgin presented with severe menorrhagia and a haemoglobin level of 76 g/L as a problem of management. A 5 cm diameter submucous fibroid was identified at hysteroscopy and biopsied but was unable to be removed. The luteinising hormone releasing hormone agonist, buserelin, was used in an attempt to produce symptomatic relief. One week after commencing buserelin therapy, severe menorrhagia occurred and the patient was admitted to hospital with a haemoglobin concentration of 24 g/L. Buserelin treatment was continued and no further menstruation occurred over the following year. As the patient was now well, hysteroscopic submucous fibroid resection was contemplated. Due to cervical rigidity in this teenager, a 1 mg gemeprost pessary was inserted into the posterior vaginal fornix three hours before surgery. This allowed an operative hysteroscope to be inserted into the uterus and a fibroid resection to be performed. Menstrual blood loss has been normal for six months after hysteroscopy. A combined medical and surgical approach may avoid hysterectomy in such problem patients.

Adult↗
PubMed1991

A controlled study of gonadotropin-releasing hormone agonist (buserelin acetate) for folliculogenesis in routine in vitro fertilization patients.

STUDY OBJECTIVE: To determine if gonadotropin-releasing hormone agonist (GnRH-a) and gonadotropin therapy could improve folliculogenesis and pregnancy rates (PRs) in women with a previously satisfactory response to clomiphene citrate and human menopausal gonadotropin (hMG). DESIGN: Randomized prospective study. SETTING: Assisted reproduction clinic. PATIENTS: One hundred fifty-seven women were randomized to receive either hMG alone or the GnRH-a buserelin acetate 600 microgram/d or buserelin acetate 1,200 microgram/d plus hMG. RESULTS: Compared with hMG alone, pretreatment with buserelin acetate significantly increased the PR per cycle started by preventing a premature luteinizing hormone rise and thereby reducing the number of abandoned cycles. There was, however, no difference between the number of follicles aspirated, oocytes obtained, or fertilization rates between groups. Furthermore, agonist therapy significantly increased both the dose of hMG required and the duration of stimulation. CONCLUSION: The routine use of GnRH-a in in vitro fertilization programs must be questioned.

Buserelin↗
PubMed1991

Endometrial prolactin and implantation.

The role of prolactin in human implantation and human endometrial function is still unclear. Synthesis of prolactin from human endometrium and decidua was first demonstrated in 1977. Prolactin mRNA isolation from term decidua subsequently confirmed expression of the prolactin gene in human endometrium. More recently, a glycosylated form of prolactin has been isolated from both the human pituitary and human endometrium. It appears that predominately glycosylated prolactin is secreted in the late luteal phase of the menstrual cycle, with increasingly greater amounts of non-glycosylated prolactin secreted as pregnancy advances. The biological significance and regulation of prolactin glycosylation is uncertain, although glycosylated ovine prolactin has only 20-33% of the lactogenic activity of ovine prolactin. Pituitary lactotropes, of ectodermal origin, produce pituitary prolactin and are regulated by dopamine, oestradiol and thyrotropin releasing hormone. Decidual cells, of mesodermal origin, are not influenced by these pituitary secretogogues. Progesterone and calcium both appear to stimulate pituitary and decidual prolactin secretion, while arachidonic acid seems to inhibit decidual prolactin release. More recently, insulin like growth factor-1, a polypeptide growth factor implicated in the oestrogen promoted growth reproductive tissues, has been found in high concentration in the pig uterus and has been shown to stimulate the synthesis and secretion of prolactin from human decidua. Prolactin receptors have not been reported on endothelium of blood vessels and no clear evidence exists that endometrial prolactin may modulate the secretion of endothelin, endothelium derived relaxing factor or other potentially important substances controlling menstruation. Prolactin does appear necessary for the normal production of macrophage activating factors, including interferon, and may have a local immunomodulatory role upon human implantation for this reason. Human alpha 2-interferon has sequence homology to ovine trophoblast protein-1 and is found in high concentration in human pregnancy and fetal tissues. There is some evidence that interferon may reduce human endometrial prolactin secretion, but whether endometrial or decidual prolactin is critical to human implantation awaits further study.

Animals↗
PubMed1991

Concentrations of immunoactive inhibin in serum during human pregnancy: evidence for an ovarian contribution.

Immunoactive inhibin (ir-inhibin) concentrations in maternal serum during normal human pregnancy have been established in two separate studies employing cross-sectional and longitudinal sampling regimes. Ir-inhibin concentrations rose from the mid-luteal phase (geometric mean + 95% confidence intervals 1.490 (1.086-2.028) U mL-1) to peak at week 11 of gestation (3.77 (3.26-4.35) U mL-1), declined to a plateau from 14 to 25 weeks with means ranging from 1.8 to 2.3 U mL-1, and subsequently rose slowly to a peak of 6.53 U mL-1 at 41 weeks. In the longitudinal study, similar results were obtained and no differences were found in maternal inhibin levels in women carrying male or female fetuses. Paired cord blood and maternal samples showed no significant difference in ir-inhibin concentrations irrespective of the sex of the fetus. However, in all such pregnancies amniotic fluid ir-inhibin levels were 2-3 fold greater than maternal or fetal levels raising the possibility that the amnion may secrete inhibin. In 12 women without functional ovaries in whom a singleton pregnancy was achieved by donation of oocytes and in vitro fertilization, the ir-inhibin levels showed a similar pattern in the first trimester of pregnancy but the concentrations achieved were markedly lower (peak 1.1 U mL-1 at 9 weeks). In five women from the group in whom samples were available late in gestation, three showed greater than normal levels and two had subnormal levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Amniotic Fluid↗