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Biomedical subjects

P Hardiman

Publications and source records attributed to P Hardiman.

At least 19 recordsLinked to original sources
PubMed1998

Uterine artery blood flow parameters in women with dysfunctional uterine bleeding and uterine fibroids: the effects of tranexamic acid.

The objective of this study was to investigate the effects of tranexamic acid on uterine vascular resistance in women with dysfunctional uterine bleeding and in women with menorrhagia associated with fibroids. A longitudinal, prospective study was carried out in premenopausal women referred to a gynecological outpatient department with a complaint of menorrhagia. We studied 24 women with dysfunctional uterine bleeding (mean age 38.8 years; normal ultrasound examination, hysteroscopy and endometrial biopsy) and 12 women (mean age 42.8 years) with at least one fibroid greater than 2.0 cm on ultrasound examination. None were on any form of oral contraception or other medication which could influence uterine vascular resistance. All women had normal coagulation and thyroid function tests. Transvaginal scanning was performed using an Aloka SSD 650 machine with a 5-MHz probe and pulsed Doppler. Pulsatility index (PI) and resistance index (RI) were measured from the left and right uterine arteries before and during the second month of treatment with tranexamic acid (1 g orally three times a day). Menstrual blood loss was assessed using a validated pictorial blood chart. In women with dysfunctional uterine bleeding, the mean PI and RI fell significantly with treatment (PI 2.20-1.94, p = 0.0001; RI 0.81-0.77, p = 0.003). There was a reduction of approximately 30% in menstrual blood loss with treatment (210.0-137.6 ml, p = 0.0001). In women with uterine fibroids, there was no significant change in either the PI or the RI with treatment and there was no significant reduction in menstrual blood loss. We conclude that tranexamic acid significantly reduces uterine artery vascular resistance in women with dysfunctional uterine bleeding. This effect is unlikely to be a mechanism for the action of tranexamic acid in reducing menstrual blood loss but may have important implications for women taking this treatment in the long term.

Adult↗
PubMed1996

IGFBP-1 in the placenta, membranes and fetal circulation: levels at term and preterm delivery.

Samples of maternal blood, amniotic fluid, placenta, fetal membranes and umbilical venous blood were collected from 59 women at vaginal delivery (32-41 weeks gestation) and 15 women at delivery by Caesarean section (37-41 weeks gestation). Umbilical vein levels of IGFBP-1 were significantly lower in deliveries prior to the onset of labour (elective Caesarean section) than those during normal vaginal delivery. These levels were, in turn, significantly lower than those delivered by emergency Caesarean section. This difference was not seen in any of the other tissues examined. Concentrations of IGFBP-1 were lower in placenta and membrane extracts from preterm deliveries than in term deliveries. This difference was not observed in maternal or fetal serum or in amniotic fluid. This study confirms that the fetal membranes are a major source of IGFBP-1 and that fetal circulating levels are raised where there is evidence of fetal hypoxia. The absence of a comparable rise in levels in placenta, membranes or amniotic fluid suggests that the origin of this increase is from fetal tissue.

Amniotic Fluid↗
PubMed1996

Measurement of interleukin-1 alpha and interleukin-6 in pregnancy-associated tissues.

The concentrations of interleukin-1 alpha (IL-1 alpha) and IL-6 in pregnancy-associated tissues were investigated in term labour and delivery in the absence of labour (elective Caesarean section). Samples of amniotic fluid, placenta, fetal membranes, umbilical venous and, where possible, umbilical arterial blood were collected at delivery (37-41 weeks of gestation). Maternal blood was sampled during labour. Fluid and tissue extracts were assayed for IL-1 alpha and IL-6 by radioimmunoassay. Placenta and membranes were examined histologically for evidence of infection. Concentrations of IL-1 alpha and IL-6 in amniotic fluid and membrane extract, and IL-1 alpha in maternal and fetal blood, were raised after the onset of labour. Concentrations of both cytokines in the placenta remained unchanged. There was a good correlation between concentrations of both cytokines in amniotic fluid and membranes. There was also a significant correlation between concentrations of IL-1 alpha and IL-6 in amniotic fluid, placenta and membranes. It is suggested that the fetal membranes or maternal decidua, but not the placenta, internal fetal or maternal tissues, are the main sources of IL-1 alpha and IL-6 during labour.

Amniotic Fluid↗
PubMed1995

The effects of the somatostatin analogue octreotide on ovulatory performance in women with polycystic ovaries.

The elevated luteinizing hormone (LH) and androgen concentrations characteristic of women with polycystic ovaries (PCO) are considered crucial factors in their infertility. The somatostatin analogue octreotide lowers LH and androgen concentrations in women with PCO. The effects of octreotide given concurrently with human menopausal gonadotrophin (HMG) were therefore compared with that of HMG alone in 28 infertile women with PCO resistant to clomiphene. In 56 cycles of combined HMG and octreotide therapy there was more orderly follicular growth compared with the multiple follicular development observed in 29 cycles in which HMG was given alone (mean number of follicles > 15 mm diameter on the day of human chorionic gonadotrophin (HCG) administration: 2.5 +/- 0.2 and 3.6 +/- 0.4 respectively; P = 0.026). There was a significantly reduced number of cycles abandoned (> 4 follicles > 15 mm diameter on day of HCG) in patients treated with octreotide+HMG, so that HCG had to be withheld in only 5.4% of cycles compared to 24.1% with HMG alone (P < 0.05). The incidence of hyperstimulation was also lower on combined treatment. Octreotide therapy resulted in a more 'appropriate' hormonal milieu at the time of HCG injection, with lower LH, oestradiol, androstenedione and insulin concentrations. Although growth hormone concentration was similar on both regimens, significantly higher insulin growth factor-I concentrations were observed on the day of HCG in women on combined therapy than on HMG alone.

Adult↗
PubMed1992

Effects of the somatostatin analogue, octreotide, in polycystic ovary syndrome.

In view of the association of hyperinsulinemia with elevated luteinizing hormone (LH) levels and hyperandrogenism in polycystic ovary syndrome (PCOS), the effect of octreotide was investigated in women with PCOS. Twelve amenorrheic women were treated with 100 micrograms octreotide twice a day for 7 days; 13 infertile women unresponsive to clomiphene citrate were treated either with octreotide (100 micrograms twice a day from day 1 of the menstrual cycle until corpus luteum formation) in addition to human menopausal gonadotropins (HMG) or with HMG alone. Octreotide significantly reduced the 4-hour integrated LH concentrations. LH pulse amplitude and nadir concentrations, and LH, testosterone, androstenedione, and estradiol responses to a gonadotropin-releasing hormone (GnRH) analogue in amenorrheic PCOS women. Octreotide treatment also resulted in a more "appropriate" hormonal milieu at the time of human chorionic gonadotropin (HCG) injection in the infertile women, with LH and testosterone levels being reduced while follicle-stimulating hormone (FSH) levels increased. Orderly follicular growth occurred, with one or two mature follicles being present at the time of HCG injection in cycles in which octreotide was given together with HMG. There were no cases of hyperstimulation, even in women who had previously hyperstimulated after HMG alone. Octreotide thus inhibits LH and androgen secretion and may improve ovulatory performance in infertile women with PCOS.

Adolescent↗
PubMed1992

Vaginal bromocriptine--clinical and biochemical effects.

Adverse effects occur in over 50% of women taking oral bromocriptine, causing at least 10% to discontinue treatment. Although the drug is absorbed from the vagina and reportedly caused no side-effects in one patient intolerant of oral bromocriptine, long-term clinical effects of daily vaginal administration have not been assessed. We have now given bromocriptine vaginally for up to 2 years to 31 hyperprolactinemic and five normoprolactinemic women, 17 of whom were intolerant of oral bromocriptine. The drug was well absorbed from the vagina and a daily dosage of 2.5 mg lowered serum prolactin levels in 28 of the hyperprolactinemic women (in 11 to within normal limits), restored menstrual cyclicity, and abolished galactorrhea; one of the four infertile women conceived. Minor side-effects occurred in only three women. Vaginal administration is clinically effective, avoids the adverse effects of oral therapy and could be the first-line treatment for patients requiring bromocriptine.

Administration, Intravaginal↗
PubMed1991

Cardiovascular effects of Org OD 14--a new steroidal therapy for climacteric symptoms.

The cardiovascular effects of Org OD 14, a synthetic steroid which relieves climacteric symptoms without stimulating the endometrium, were assessed in a group of healthy post-menopausal women. Limb blood flow was measured by venous occlusion plethysmography. Resting forearm blood flow, the dilator response to anoxic exercise and heart rate increased significantly after six weeks of drug treatment. Hand flow was unchanged. The cardiovascular effects of Org OD 14 differ from those seen with oestrogens, in keeping with the unique pharmacological profile of this steroid.

Blood Pressure↗
PubMed1991

Ovulation induction with human menopausal gonadotropins--a changing scene.

The aim of human menopausal gonadotropin treatment (hMG), to simulate normal follicular development by injecting FSH and LH and induce follicular rupture with hCG, is rarely met. Multiple follicular development occurs because hypothalamic-pituitary feedback is bypassed. This, exacerbated by the long half-life of hCG, causes the principal complications of hMG therapy--multiple pregnancy and hyperstimulation. The initial use of hMG in pituitary deficiency has been widened to include failure to respond to clomiphene, polycystic ovaries, 'unexplained infertility' and in vitro fertilization. Reported pregnancy rates, incidence of hyperstimulation and of multiple pregnancy vary widely. We reviewed the results of hMG therapy from 1977 to 1989 in 260 consecutive women with clomiphene-resistant infertility. Conception and live birth rates after six treatment cycles were 45.7% and 43.3%, respectively and were influenced by the cause of infertility, age, weight and sperm parameters. The miscarriage rate was 18.6% and multiple pregnancy rate 19.3%. The conception rate fell during the 12-year period in all groups except those with regular anovulatory cycles. Over this period, age, weight and male subfertility increased in patients referred to us. hMG is an effective and safe treatment for women with clomiphene-resistant infertility and patent tubes.

Adult↗
PubMed1990

Are estrogen assays essential for monitoring gonadotropin stimulant therapy?

Ovarian responses to human menopausal gonadotropin (hMG) are conventionally monitored by urinary estrogen or serum estradiol (E2) concentration. E2 can also be measured in saliva but this is rarely used. With ultrasound (USS) however, follicular development is assessed directly and we have previously shown that USS is superior to urinary estrogens for monitoring. We have now compared salivary and serum E2 with USS during hMG therapy in 48 women over 101 cycles. Salivary and serum E2 correlated significantly with each other and with the number of mature follicles. The manufacturers of hMG state that hCG should be given only when E2 is between 100 and 3000 pmol/l. However, there were no mature follicles in 40% of the cycles where E2 lay within this range. USS is the most accurate method of monitoring responses to hMG and, where this is available, estrogen assay provides no additional useful information.

Estradiol↗
PubMed1989

Peripheral blood flow in menopausal women who have hot flushes and in those who do not.

OBJECTIVE: To compare blood pressure, heart rate, and peripheral vascular responsiveness in menopausal women who have hot flushes and in those who do not, and to assess the effect on these variables of treating women who have hot flushes with oestriol, a natural oestrogen, given vaginally. DESIGN: An open, non-randomised cohort study of flushing and non-flushing menopausal women. A before and after investigation of the effects of vaginal oestriol treatment on the circulation. SETTING: Referral based endocrinology clinic. PATIENTS: 88 Consecutive menopausal women, 63 complaining of frequent hot flushes and 25 who had not flushed for at least a year. INTERVENTION: Treatment with vaginal oestriol 0.5 mg at night for six weeks in 18 of the women who had hot flushes. MEASUREMENTS AND MAIN RESULTS: Peripheral blood flow was measured by venous occlusion plethysmography at rest and in response to stressful mental arithmetic and anoxic forearm exercises. Blood flow in the forearm and its variability were significantly higher in flushing than in non-flushing women (4.1 (SD 1.7) and 3.1 (0.9) ml/100 ml tissue/min and 17% and 13% respectively). Blood pressure, heart rate, and blood flow in the hand were, however, similar in the two groups. No difference was found in the peripheral incremental response to either stress or anoxic exercise. Vaginal oestriol significantly lowered forearm blood flow from 4.4 (1.5) to 3.3 (1.1) ml/100 ml tissue/min but dilator responsiveness was unaffected. CONCLUSIONS: The peripheral circulation is different in menopausal women who have hot flushes compared with those who do not, with selective vasodilatation in the forearm. The lowered blood flow in the forearm after vaginal oestriol in flushing women may be relevant to the alleviation of vasomotor symptoms induced by oestrogen treatment.

Administration, Intravaginal↗