Search PubMed⌕ Search

Biomedical subjects

A Templeton

Publications and source records attributed to A Templeton.

At least 91 records · Page 5Linked to original sources
PubMed1996

The effects of steroidal and non-steroidal ovarian hormones on pituitary responsiveness to gonadotrophin surge-attenuating factor.

Primary pituitary cultures from adult female rats were used to investigate the effects of steroidal (oestradiol and progesterone) and non-steroidal (inhibin, follistatin) ovarian hormones on the suppressive actions of the ovarian factor gonadotrophin surge-attenuating factor (GnSAF) in the control of gonadotrophin secretion. The source of GnSAF was a chromatographic preparation from follicular fluid containing four distinct protein bands as resolved on SDS-PAGE. Oestradiol and progesterone added alone had no effect on gonadotrophin secretion but had a wide range of effects on the suppression of both LH and FSH secretion caused by the non-steroidal factors. Oestradiol, progesterone and oestradiol+progesterone enhanced the suppressive actions of GnSAF on GnRH-induced LH secretion (causing 19.3 +/- 5.2% (P < 0.05), 41.9 +/- 3.4% (P < 0.001) and 32.2 +/- 5.3% (P < 0.001) greater suppression than GnSAF alone). Progesterone and oestradiol+progesterone completely abolished the suppression of basal FSH secretion caused by inhibin (causing 157.1 +/- 22.2%, P < 0.001, and 160.9 +/- 11.3%, P < 0.001, stimulation compared with inhibin alone). Separately the steroids had no effect on the suppression of gonadotrophin secretion caused by follistatin. However, in combination, oestradiol+progesterone potentiated the suppressive actions of follistatin on GnRH-induced LH secretion causing 29.9 +/- 5.3% (P < 0.05) greater suppression than follistatin alone. In combination, high-dose follistatin and GnSAF caused 31.1 +/- 6.5% (P < 0.01) greater suppression than GnSAF alone. Thus in combination high-dose follistatin and GnSAF have additive effects on the suppression of GnRH-induced LH secretion. Recombinant human inhibin and GnSAF added in combination had little further effect compared with either alone suggesting that they may have a similar mechanism of action at the pituitary level. These results demonstrate that while FSH secretion in vitro is mainly controlled by inhibin and follistatin, LH secretion is affected by the presence of a whole range of factors. We have demonstrated that oestradiol and progesterone potentiate the suppressive actions of GnSAF in vitro. These data are compatible with the suggestion that in the late follicular phase it is falling levels of GnSAF that allow positive feedback of the steroids on the pituitary to elicit the LH surge, rather than increases in the stimulatory effects of the ovarian steroids overcoming GnSAF. The actions of GnSAF on the pituitary may be modulated by follistatin but it is unlikely that inhibin has any modulatory effects on the GnSAF-induced suppression of LH secretion.

Animals↗
PubMed1995

Induction of abortion with mifepristone (RU 486) and oral or vaginal misoprostol.

BACKGROUND: Medical termination of pregnancy can be successfully performed with a combination of mifepristone (RU 486) and a prostaglandin analogue. We conducted a prospective, randomized trial to compare oral with vaginal administration of the prostaglandin E1 analogue misoprostol for first-trimester abortion in women treated initially with mifepristone. METHODS: The study population consisted of 270 women seeking abortion within 63 days after the onset of amenorrhea. The dose of mifepristone was 600 mg, and the dose of misoprostol was 800 micrograms. The study had two primary end points: expulsion of the conceptus without the need for a surgical procedure, and abortion within four hours after the administration of misoprostol. RESULTS: Expulsion of the conceptus without the need for a surgical procedure occurred in 95 percent of the women who received misoprostol vaginally and in 87 percent of those who received it orally (P = 0.03). The rate of continued pregnancy was 7 percent with the oral regimen and 1 percent with the vaginal regimen (P = 0.01). Ninety-three percent of the women receiving misoprostol vaginally had abortions within four hours, as compared with only 78 percent of the women receiving the drug orally (P < 0.001). Vomiting and diarrhea were reported more frequently by the women who received oral misoprostol than by those who received vaginal misoprostol (P = 0.04 and P = 0.002, respectively). CONCLUSIONS: After the administration of mifepristone, vaginal administration of misoprostol is more effective and better tolerated than oral administration for the induction of first-trimester abortion.

Abortion, Induced↗
PubMed1995

Nef and LTR sequence variation from sequentially derived human immunodeficiency virus type 1 isolates.

Variation in HIV-1 nef and LTR DNA sequences was assessed longitudinally during disease progression in four HIV-1-infected subjects. Point mutations were found among quasispecies obtained at a single time point in each individual, with increasing diversity with disease progression in two of three patients for whom sufficient data were available for analysis. Deletions and rearrangements were more common in late than early stages of disease. Continued sequence evolution in HIV-1 quasispecies with nef deletions along with coexistence of nef-bearing quasispecies suggest that nef-deleted quasispecies are capable of replication in vivo, possibly complemented by quasispecies lacking such deletions and/or by adaptation to a specialized niche within the patients.

Amino Acid Sequence↗
PubMed1995

Antenatal screening for carriers of cystic fibrosis: randomised trial of stepwise v couple screening.

OBJECTIVE: To perform a rigorous comparative evaluation of stepwise and couple approaches to antenatal carrier screening for cystic fibrosis. DESIGN: Pragmatic randomised trial. SETTING: Hospital antenatal clinic serving a regional population. SUBJECTS: 2002 women (couples) attending for booking antenatal visit at less than 17 weeks' gestation with no family history of cystic fibrosis. INTERVENTIONS: Offering counselling and carrier testing for cystic fibrosis, either to women in the first instance (stepwise) or to couples (couple screening). MAIN OUTCOME MEASURES: Uptake rates; anxiety; knowledge of cystic fibrosis and carrier status (both partners); attitudes to health, pregnancy, the baby, and screening (both partners); and uptake of carrier testing by relatives. RESULTS: Uptake of screening was the same for both approaches (90%). After delivery most women remembered test results and their meaning, but 53/253 (21%) of those with negative results of couple testing had forgotten that repeat testing would be advisable if they had a pregnancy with a new partner. With stepwise screening women identified as carriers had high levels of anxiety when results were received (mean anxiety score 52.3). This dissipated with a reassuring partner's result (carriers' mean anxiety score 36.1) to levels similar to those receiving negative results from couple screening. Of those receiving negative results, women who had stepwise screening were significantly less anxious than those who had couple screening (mean score with result 32.1 v 35.4, 95% confidence interval for difference -4.7 to -2.1). CONCLUSIONS: Couple screening allows carriers to avoid transient high levels of anxiety, but is associated with more anxiety and false reassurance among most screenees who will test negative. Stepwise screening gives carriers and their relatives genetic information and is, in our opinion, the better method.

Anxiety↗
PubMed1995

Gonadotrophin surge-attenuating factor bioactivity is present in follicular fluid from naturally cycling women.

Rat pituitary monolayer bioassays were used to compare gonadotrophin surge-attenuating factor (GnSAF) bioactivity in follicular fluid from 12 follicles in 10 spontaneously cycling women with that in pooled follicular fluid from women undergoing ovulation induction. Expressed as ED50S (microliter follicular fluid/well producing 50% of maximal effect), GnSAF bioactivity was detectable in all spontaneous follicular fluid samples (1.4-33.3 microliters/well) and in follicular fluid from women undergoing ovulation induction (6.8 microliters/well). This GnSAF bioactivity was unaffected by pre-incubation with an inhibin antibody. When the data were grouped according to whether the recovered oocytes fertilized in vitro or not, the fertilized group contained significantly greater GnSAF bioactivity than the unfertilized group (5.3 +/- 1.1 and 14.1 +/- 2.6 microliters/well respectively, P < 0.05). While both inhibin bioactivity (9.7 +/- 1.4 and 28.9 +/- 12.1 microliters/well) and immunoreactivity (36.8 +/- 2.2 and 21.0 +/- 3.0 and ng/ml) were also greater (P < 0.01) in the fertilized compared with the unfertilized groups respectively, there were no other significant differences between the two groups. We conclude that GnSAF is found in follicular fluid from spontaneously cycling women, supporting in-vivo evidence for the involvement of GnSAF in feedback control of the ovary-pituitary axis.

Adult↗
PubMed1995

Current attitudes towards egg donation among men and women.

Recent widespread concern has led to legislation in the UK preventing the use of fetal ovarian tissue for the treatment of infertile women. This questionnaire-based study aimed to assess the attitudes of both fertile and infertile men and women as well as egg donors and recipients towards the use of donated eggs for treatment, diagnosis and research. Fertile individuals were significantly less aware of egg donation but the majority in both the fertile and the infertile groups approved the use of eggs for research (89 and 95% of women and 88 and 92% of men respectively) and treatment (similar percentages). However, fetal sources of oocytes were acceptable to only 15% of women in the fertile, 21% in the infertile, 35% in the recipient and 19% in the donor groups. Cadaveric sources of oocytes were slightly more acceptable (28% fertile, 28% infertile, 50% recipient and 42% donors). Both these sources of oocytes were slightly more acceptable to men. Education had little influence on attitudes, although men and women of tertiary education level said they would be less likely to have gamete donation themselves. Thus there would appear to be widespread approval for the use of donor eggs in research and treatment but not if the source of eggs is fetal or cadaveric.

Aborted Fetus↗
PubMed1995

Cryopreservation of human oocytes and fertilization by two techniques: in-vitro fertilization and intracytoplasmic sperm injection.

Human oocyte cryopreservation results in poor survival and subsequent fertilization rates. It has been suggested that freeze-thaw-induced changes in the zona pellucida may impair sperm penetration or attachment. The aim of this study was to compare fertilization and cleavage rates in cryopreserved oocytes inseminated by conventional in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). A total of 220 oocytes, obtained from volunteers who had undergone ovarian stimulation, were cryopreserved using a slow freeze-rapid thaw protocol with 1.5 M propanediol as the cryoprotectant. Surviving oocytes (n = 74, 34.4%) were randomly allocated for fertilization by conventional IVF (group 1) or ICSI (group 2) using cryopreserved spermatozoa from a single donor of proven fertility. Fertilization was achieved in five (13.5%) of the oocytes in group 1 and 17 (45.9%) in group 2 (P < 0.005), with only one oocyte in group 1 exhibiting normal fertilization as opposed to 16 (43.2%) in group 2 (P < 0.001). Similarly, one oocyte fertilized by IVF cleaved, while all fertilized with ICSI cleaved (P < 0.001). We conclude that although the survival of oocytes is poor following cryopreservation, fertilization and cleavage rates can be enhanced significantly using ICSI. These data also suggest that the method of cryopreservation used in this study affected the zona pellucida, such that normal sperm attachment or penetration was impaired.

Cleavage Stage, Ovum↗
PubMed1995

Induction of abortion in the second trimester by a combination of misoprostol and mifepristone: a randomized comparison between two misoprostol regimens.

The combination of mifepristone (RU486) and prostaglandin is effective in the induction of abortion in the second trimester. The optimal regimen is still under development, but is likely to be characterized by a short induction-to-abortion interval, low incidence of side-effects and high acceptability. We have investigated further whether misoprostol, a synthetic prostaglandin E1 analogue, can reliably induce second trimester abortion in 70 women pre-treated with mifepristone, and whether different routes of administration affect the induction-to-abortion interval. Abortion was achieved in 97% [95% confidence interval (CI) 90-100%] of cases without resort to other prostaglandin agents. The mean induction abortion time for the studied population was 6.4 h (95% CI 5.6-7.0 h). No significant difference was found between two different routes of administration, namely vaginal versus a combination of vaginal and oral. Misoprostol has a number of advantages over other prostaglandin preparations. We recommend that, following pre-treatment with mifepristone, misoprostol is used as the prostaglandin of choice to induce abortion in the second trimester.

Abortion, Induced↗
PubMed1995

A comparison of the effects of different biopsy strategies on the post-thaw survival of 8-cell-stage mouse embryos: implications for preimplantation diagnosis.

The aim of this study was to investigate the effects of two different biopsy strategies, zona slitting and zona piercing, on the post-thaw survival and subsequent in-vitro development of 8-cell mouse embryos. From control experiments it was determined that neither biopsy by zona slitting nor zona piercing adversely affected embryo development in vitro, as similar rates of blastocyst formation and hatching were found between biopsied and zona-intact embryos; there was, however, a trend towards a lower rate of blastocyst hatching in embryos biopsied by zona piercing (78.3% compared with 91.9% of zona-intact embryos). When biopsy was followed by cryopreservation a different picture was seen: similar rates of freeze-thaw survival were found for zona-slit, zona-pierced and zona-intact embryos (84.2, 88.5 and 87.2% respectively), but this was superseded by a significant (P < 0.05) reduction in the blastocyst formation rates (61.4% zona-slit and 63.9% zona-pierced versus 78.7% zona-intact) and hatching rates (51% zona-slit and 52.5% zona-pierced versus 72.3% zona-intact) of the biopsied embryos. When the effects of zona slitting and piercing were considered in isolation, i.e. without performing biopsy, it was found that the larger holes produced by zona slitting rendered embryos more susceptible to freeze-thaw damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Gonadotropin surge-attenuating factor bioactivity in serum from superovulated women is not blocked by inhibin antibody.

Primary pituitary cultures from adult female rats were used to investigate gonadotropin surge attenuating factor (GnSAF) bioactivity. Serum from superovulated women was charcoal-treated and incubated with either an inhibin antibody (MC4), normal sheep serum (NSS), or serum-free defined medium (SFDM) before addition to cell culture. The reduction in GnRH-induced LH secretion (GnSAF bioactivity) produced by the serum (30.1 +/- 6.5%, p < 0.001, of control) was not altered by prior incubation with either MC4 or NSS (24.9 +/- 3.6 and 23.2 +/- 2.7%, p < 0.001, of control, respectively). This indicates that GnSAF bioactivity present in serum from superovulated women is not entirely attributable to inhibin. Recombinant human inhibin reduced basal FSH secretion to 24.6 +/- 4.7% (p < 0.001) of the control value. However, this was totally abolished by prior incubation with MC4, but not NSS. We have also shown that ovarian steroids are not responsible for GnSAF bioactivity in vitro. In conclusion, in contrast to findings in superovulated rats, inhibin antibody did not block GnSAF bioactivity in serum from superovulated women.

Animals↗
PubMed1995

Contractile responses to sumatriptan in isolated bovine pulmonary artery rings: relationship to tone and cyclic nucleotide levels.

We examined responses to the 5-hydroxytryptamine 1D (5-HT1D)-receptor agonist sumatriptan in bovine pulmonary artery rings (2-3 mm ID). The effects of agonist-induced tone and agents that alter intracellular cyclic AMP [cyclic AMP]i or [cyclic GMP]i on responses to sumatriptan were investigated. At resting tension, responses to sumatriptan were slight or not evident. In the presence of tone induced by U46619, responses to sumatriptan (1 nM-30 mM) were greatly potentiated, as were responses to the alpha2-adrenoceptor agonist UK14304. Responses to the alpha 1-adrenoceptor agonist phenylephrine (PE) were potentiated only slightly. In the presence of U46619, addition of the adenylyl cyclase activator, forskolin (1 nM-0.1 microM or isoprenaline (ISO 1 microM) induced relaxations and increases in [cyclic AMP]i and resulted in further potentiation of the contractile response to sumatriptan. Addition of 0.1 microM sodium nitroprusside (SNP) inhibited sumatriptan-induced contractions. Whereas sumatriptan alone did not significantly affect [cyclic AMP]i, in the presence of U46619 it decreased [cyclic AMP]i. This effect of sumatriptan was further enhanced in the presence of forskolin. Sumatriptan increased [cyclic GMP]i. Using a nitric oxide (NO) synthase inhibitor and vessels denuded of endothelium, we showed that the increased [cyclic GMP]i in response to sumatriptan was endothelium-dependent and mediated by NO. This increase in [cyclic GMP]i was not observed in the presence of U46619. By measuring cyclic AMP and cyclic GMP phosphodiesterase (PDE) levels, we demonstrated that the point of "cross-talk" between cyclic nucleotides may not be at the level of total PDE activity. These results highlight the important role of [cyclic AMP], [cyclic GMP]i, and endothelium function in the control of 5-HT1D receptor-mediated vasoconstriction, which is dependent on a decrease in [cyclic AMP]i in the absence of an increase in [cyclic GMP]i.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Postnatal maternal morbidity: extent, causes, prevention and treatment.

OBJECTIVE: To describe the prevalence and causes of postnatal maternal morbidity. DESIGN: Questionnaire survey of postnatal patients. Further data extracted from SMR1 returns, case records and the Aberdeen Maternity and Neonatal Databank. SETTING: Postnatal care in a teaching maternity hospital, midwife delivery hospital, general practitioner maternity units and in the community. SUBJECTS: Twenty percent random sample of deliveries (1249 women) surveyed one week, eight weeks and 12 to 18 months after delivery. MAIN OUTCOME MEASURES: Incidence of self reported maternal morbidity, treatment received, readmission rates and causes for readmission. RESULTS: Of mothers in the sample 85% (99% CI 82-88%) reported at least one health problem in hospital, rising to 87% (84-90%) of those at home; 76% (71-81%) reported at least one health problem after eight weeks post-delivery. CONCLUSIONS: Maternal morbidity is extensive and under-recognised after delivery. Measures to reduce and alleviate it must be sought.

Community Health Services↗
PubMed1995

Impact of a national audit project on gynaecologists in Scotland.

The objectives of the study were (a) to determine consultant gynaecologists' awareness of and views on a national audit project (the gynaecology audit project in Scotland) and (b) to measure changes in their reported practice in relation to 12 specific elements of care related to three audit topics (induced abortion, endometriosis, and vulvar carcinoma) for which recommendations for change had been made within the project. The study comprised a postal questionnaire survey of all 128 consultant gynaecologists in NHS practice in Scotland. The response rate was 90%. Of the respondents, 96% (109/113) recalled receiving feedback material from the audit project team and around 75% (range 66/89 to 84/105) had retained feedback reports for future reference. For the two more common clinical topics (induced abortion and endometriosis), over two thirds of the respondents indicated that they had been prompted to reconsider or change aspects of practice. Significant changes in reported practice, in line with project recommendations, were found for seven of the 12 specific elements of care examined. Thus, gynaecologists in Scotland showed a high level of awareness of and positive views towards a national audit project. Significant changes in reported practice, in accordance with circulated recommendations, were measurable in relation to several elements of clinical care.

Abortion, Induced↗
PubMed1995

Infertility-epidemiology, aetiology and effective management.

Current epidemiological evidence suggests that 15% of couples will experience infertility and in half this number the problem will remain unresolved. Background prevalence rates now appear to be reasonably stable, but there is evidence of an increase in the rate of referrals for medical help. Rates of secondary infertility are higher in the population than represented by clinic referrals. The distribution of the main diagnostic groups is as follows: Male 25%; Ovulation 25%; Tubal 20%; Unexplained 25%; and Endometriosis 5%. Effective management in the male includes donor insemination and assisted reproduction (including intra-cytoplasmic sperm injection). Drugs are ineffective for idiopathic oligozoospermia, while the role of varicocele ligation is uncertain, but marginal at best. Ovulation problems can be treated with a high degree of success, except in cases of clomiphene resistant polycystic ovarian disease. However there are continuing concerns over multiple pregnancy rates and future research is needed to clarify the additional risks, if any, of ovarian carcinoma. Surgical correction of tubal abnormalities should be left to specialised units, where audit indicates that the results can match those achieved by assisted reproduction. There is no evidence that the medical (drug) management of endometriosis improves fertility, although surgery for moderate and severe disease can still be considered. However the results should be compared with those achieved by assisted reproduction. Superovulation and intra-uterine insemination appears to be an effective treatment for certain cases of mild male factor infertility, mild endometriosis and unexplained infertility and can be considered, where the duration of infertility is more than four years. A pregnancy rate of around 10% per cycle can be anticipated, but there is a significant risk of multiple pregnancy. The evidence is that IVF (and GIFT) has achieved significantly improved results in recent years, with fecundity rates of 20% per cycle being a reasonable target in women under 40 years.

Adult↗
PubMed1995

The management of carcinoma of the vulva: current opinion and current practice among consultant gynaecologists in Scotland.

A postal questionnaire survey of all 126 consultant gynaecologists in Scotland was undertaken in order to obtain an overview of current opinion and current practice in relation to the management of vulval carcinoma. The response rate was 95%. Fifteen suggested criteria for good quality care were validated by a balance of agreement among respondents. There was particularly strong agreement (> 90% of respondents) that vulval carcinoma should be managed by subspecialists rather than generalists, that en bloc radical vulvectomy is not always required, that patients should be informed of their diagnosis and that long-term follow-up is required. There was least agreement (< 50% of respondents) that groin lymphadenectomy may be omitted in selected cases and that follow-up need be at special multidiscipline clinics. An encouraging picture of current practice emerged. Very few consultants who do not profess to be oncology subspecialists would manage cases alone, few perform en bloc radical vulvectomy in all cases and few undertake deep pelvic lymphadenectomy. Most acknowledge the importance of psychosexual issues and all generally inform patients of the nature of their diagnosis. The postal questionnaire approach achieved a good response rate and has provided an informative overview of current opinion and practice on a national basis. This approach may be more valuable than case-note review audit in providing a meaningful picture of contemporary practice for uncommon conditions like vulval cancer.

Clinical Protocols↗
PubMed1994

Multicentre criterion based audit of the management of induced abortion in Scotland.

OBJECTIVES: To assess and improve the quality of care provided to women undergoing induced abortion. DESIGN: Two rounds of prospective, criterion based case note review audit. SETTING: Ten NHS gynaecology units throughout Scotland. SUBJECTS: 2004 patient episodes of abortion care identified consecutively during two rounds of audit. The first round comprised 967 cases and the second round 1037. INTERVENTIONS: Dissemination of results from the first round of audit and recommendations for change in the form of a written report and at postgraduate meetings in participating hospitals. MAIN OUTCOME MEASURES: Improvements in quality of care as assessed against 16 previously agreed criteria, both overall across the 10 study hospitals and within individual hospitals. RESULTS: Overall, four significant improvements occurred: increased availability of early medical abortion, decreased utilisation of surgical abortion at very early gestation, increased use of mifepristone priming before second trimester medical abortion, and increased provision of follow up. At the individual hospital level 42 of 150 elements of care studied were "close to optimal" at the time of the first round of audit, rising to 54 at the second round (NS). A total of 31 significant improvements in individual elements of care occurred, but 11 significant deteriorations also occurred (at the P < 0.05 level). CONCLUSIONS: The prospective multicentre audit proved feasible and achieved the aims of any form of audit in terms of identifying deficiencies and variations in care. The audit results prompted objective review of local abortion services in participating hospitals. At least for some elements of care in some hospitals significant improvements were detectable.

Abortion, Induced↗
PubMed1994

Cervical priming with prostaglandin E1 analogues, misoprostol and gemeprost.

Although it is well established that cervical priming before surgically induced abortion reduces the incidence of complications, its use is infrequent and confined to groups perceived to be at high risk. We compared the effect of prostaglandin E1 analogues, gemeprost and misoprostol, on the cervix. Both induced clinical and histochemical changes that were significantly different from controls and were likely to have therapeutic value. Misoprostol, however, is cheap, easily stored, and associated with few side-effects. Cervical pre-dilation with misoprostol may be considered in all women having surgically induced abortions.

Abortifacient Agents, Nonsteroidal↗